TY  - JOUR
AU  - Smiljanić, Katarina
AU  - Obradović, Milan M.
AU  - Jovanović, Aleksandra
AU  - Đorđević, Jelena D.
AU  - Dobutović, Branislava
AU  - Jevremovic, Danimir
AU  - Marche, Pierre
AU  - Isenović, Esma R.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/134
AB  - In this study, the role of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK1/2), heparin-binding EGF-like growth factor (HB-EGF), general metalloproteinases, matrix metalloproteinases-2 (MMP-2) in mediating the mitogenic action of thrombin in rat vascular smooth muscle cells (VSMC) was investigated. The incubation of rat VSMC with thrombin (1 U/ml) for 5 min resulted in significant (p LT 0.001) increase of ERK1/2 phosphorylation by 8.7 +/- A 0.9-fold, EGFR phosphorylation by 8.5 +/- A 1.3-fold (p LT 0.001) and DNA synthesis by 3.6 +/- A 0.4-fold (p LT 0.001). Separate 30-min pretreatments with EGFR tyrosine kinase irreversible inhibitor, 10 A mu M PD169540 (PD), and 20 A mu M anti-HB-EGF antibody significantly reduced thrombin-stimulated EGFR and ERK1/2 phosphorylation by 81, 72 % and by 48 and 61 %, respectively. Furthermore, the same pretreatments with PD or anti-HB-EGF antibody reduced thrombin-induced VSMC proliferation by 44 and 45 %, respectively. In addition, 30-min pretreatments with 10 A mu M specific MMP-2 inhibitor significantly reduced thrombin-stimulated phosphorylation of both EGFR and ERK1/2 by 25 %. Moreover, the same pretreatment with MMP-2 inhibitor reduced thrombin-induced VSMC proliferation by 45 %. These results show that the thrombin-induced DNA synthesis correlates with the level of ERK1/2 activation rather than EGFR activation. These results further suggest that thrombin acts through EGFR and ERK 1/2 signaling pathways involving MMP-2 to upregulate proliferation of VSMC.
T2  - Molecular and Cellular Biochemistry
T1  - Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2
VL  - 396
IS  - 1-2
SP  - 147
EP  - 160
DO  - 10.1007/s11010-014-2151-y
ER  - 

@article{
author = "Smiljanić, Katarina and Obradović, Milan M. and Jovanović, Aleksandra and Đorđević, Jelena D. and Dobutović, Branislava and Jevremovic, Danimir and Marche, Pierre and Isenović, Esma R.",
year = "2014",
abstract = "In this study, the role of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK1/2), heparin-binding EGF-like growth factor (HB-EGF), general metalloproteinases, matrix metalloproteinases-2 (MMP-2) in mediating the mitogenic action of thrombin in rat vascular smooth muscle cells (VSMC) was investigated. The incubation of rat VSMC with thrombin (1 U/ml) for 5 min resulted in significant (p LT 0.001) increase of ERK1/2 phosphorylation by 8.7 +/- A 0.9-fold, EGFR phosphorylation by 8.5 +/- A 1.3-fold (p LT 0.001) and DNA synthesis by 3.6 +/- A 0.4-fold (p LT 0.001). Separate 30-min pretreatments with EGFR tyrosine kinase irreversible inhibitor, 10 A mu M PD169540 (PD), and 20 A mu M anti-HB-EGF antibody significantly reduced thrombin-stimulated EGFR and ERK1/2 phosphorylation by 81, 72 % and by 48 and 61 %, respectively. Furthermore, the same pretreatments with PD or anti-HB-EGF antibody reduced thrombin-induced VSMC proliferation by 44 and 45 %, respectively. In addition, 30-min pretreatments with 10 A mu M specific MMP-2 inhibitor significantly reduced thrombin-stimulated phosphorylation of both EGFR and ERK1/2 by 25 %. Moreover, the same pretreatment with MMP-2 inhibitor reduced thrombin-induced VSMC proliferation by 45 %. These results show that the thrombin-induced DNA synthesis correlates with the level of ERK1/2 activation rather than EGFR activation. These results further suggest that thrombin acts through EGFR and ERK 1/2 signaling pathways involving MMP-2 to upregulate proliferation of VSMC.",
journal = "Molecular and Cellular Biochemistry",
title = "Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2",
volume = "396",
number = "1-2",
pages = "147-160",
doi = "10.1007/s11010-014-2151-y"
}

Smiljanić, K., Obradović, M. M., Jovanović, A., Đorđević, J. D., Dobutović, B., Jevremovic, D., Marche, P.,& Isenović, E. R.. (2014). Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2. in Molecular and Cellular Biochemistry, 396(1-2), 147-160.
https://doi.org/10.1007/s11010-014-2151-y

Smiljanić K, Obradović MM, Jovanović A, Đorđević JD, Dobutović B, Jevremovic D, Marche P, Isenović ER. Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2. in Molecular and Cellular Biochemistry. 2014;396(1-2):147-160.
doi:10.1007/s11010-014-2151-y .

Smiljanić, Katarina, Obradović, Milan M., Jovanović, Aleksandra, Đorđević, Jelena D., Dobutović, Branislava, Jevremovic, Danimir, Marche, Pierre, Isenović, Esma R., "Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2" in Molecular and Cellular Biochemistry, 396, no. 1-2 (2014):147-160,
https://doi.org/10.1007/s11010-014-2151-y . .

TY  - JOUR
AU  - Smiljanić, Katarina
AU  - Dobutovic, B.
AU  - Obradović, Milan M.
AU  - Nikolić, Dragana
AU  - Marche, Pierre
AU  - Isenović, Esma R.
PY  - 2011
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4468
AB  - Cardiovascular disease is the largest single cause of mortality and its major underlying pathology is atherosclerosis. The proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of the various vascular diseases, including atherosclerosis and hypertension. Thrombin (Thr) is involved in the abnormal proliferation of VSMCs associated with atherosclerosis and hypertension. ADAMs (A Disintegrin And Metalloproteinase) are transmembrane metalloproteinases, belonging to the adamalysins group, that are distinct from matrix metalloproteinases (MMPs) in a way as they have an extracellular disintegrin domain and cytoplasmic domain that can associate with intracellular proteins. There is limited knowledge about the presence of ADAM metalloproteinase activity in Thr-induced VSMCs proliferation. Therefore, this review examines recent findings in signaling mechanisms employed by Thr in modulating the regulation of proliferation of VSMCs with particular emphasis on involvement of ADAM 12 which has been identified as an important mediator of VSMCs hypertrophy and vascular diseases. These findings are critical for understanding the role of Thr in vascular biology and vascular diseases.
T2  - Current Medicinal Chemistry
T1  - Involvement of the ADAM 12 in Thrombin-Induced Rats VSMCs Proliferation
VL  - 18
IS  - 22
SP  - 3382
EP  - 3386
DO  - 10.2174/092986711796504709
ER  - 

@article{
author = "Smiljanić, Katarina and Dobutovic, B. and Obradović, Milan M. and Nikolić, Dragana and Marche, Pierre and Isenović, Esma R.",
year = "2011",
abstract = "Cardiovascular disease is the largest single cause of mortality and its major underlying pathology is atherosclerosis. The proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of the various vascular diseases, including atherosclerosis and hypertension. Thrombin (Thr) is involved in the abnormal proliferation of VSMCs associated with atherosclerosis and hypertension. ADAMs (A Disintegrin And Metalloproteinase) are transmembrane metalloproteinases, belonging to the adamalysins group, that are distinct from matrix metalloproteinases (MMPs) in a way as they have an extracellular disintegrin domain and cytoplasmic domain that can associate with intracellular proteins. There is limited knowledge about the presence of ADAM metalloproteinase activity in Thr-induced VSMCs proliferation. Therefore, this review examines recent findings in signaling mechanisms employed by Thr in modulating the regulation of proliferation of VSMCs with particular emphasis on involvement of ADAM 12 which has been identified as an important mediator of VSMCs hypertrophy and vascular diseases. These findings are critical for understanding the role of Thr in vascular biology and vascular diseases.",
journal = "Current Medicinal Chemistry",
title = "Involvement of the ADAM 12 in Thrombin-Induced Rats VSMCs Proliferation",
volume = "18",
number = "22",
pages = "3382-3386",
doi = "10.2174/092986711796504709"
}

Smiljanić, K., Dobutovic, B., Obradović, M. M., Nikolić, D., Marche, P.,& Isenović, E. R.. (2011). Involvement of the ADAM 12 in Thrombin-Induced Rats VSMCs Proliferation. in Current Medicinal Chemistry, 18(22), 3382-3386.
https://doi.org/10.2174/092986711796504709

Smiljanić K, Dobutovic B, Obradović MM, Nikolić D, Marche P, Isenović ER. Involvement of the ADAM 12 in Thrombin-Induced Rats VSMCs Proliferation. in Current Medicinal Chemistry. 2011;18(22):3382-3386.
doi:10.2174/092986711796504709 .

Smiljanić, Katarina, Dobutovic, B., Obradović, Milan M., Nikolić, Dragana, Marche, Pierre, Isenović, Esma R., "Involvement of the ADAM 12 in Thrombin-Induced Rats VSMCs Proliferation" in Current Medicinal Chemistry, 18, no. 22 (2011):3382-3386,
https://doi.org/10.2174/092986711796504709 . .

TY  - JOUR
AU  - Isenović, Esma R.
AU  - Soskić, Sanja S.
AU  - Trpković, Andreja
AU  - Dobutović, Branislava
AU  - Popović, Milan
AU  - Gluvić, Zoran
AU  - Putniković, Biljana
AU  - Marche, Pierre
PY  - 2010
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4209
AB  - Vascular smooth muscle cells (VSMC) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMC allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMC proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Signal transduction pathways in eukaryotic cells integrate diverse extracellular signals, and regulate complex biological responses such as growth, differentiation and death. One group of proline-directed Ser/Thr protein kinases, the mitogen-activated protein kinases (MAPKs), plays a central role in these signalling pathways. Much attention has focused in recent years on subfamilies of MAPKs, the extracellular signal regulated kinases (ERKs). Here we overview the work on ERKs 1 to 2, emphasising when possible their biological activities in VSMC proliferation. It is clear from numerosus studies including our own, that ERK1/ERK2 pathway has an imoprtant role in VSMC proliferation induced by insulin (INS) and thrombin. Despite the physiological and pathophysiological importance of INS and thrombin, possible signal transduction pathways involved in INS and thrombin regulation of VSMCs proliferation remains poorly understood. Thus, this review examines recent findings in signalling mechanisms involved in INS and thrombin-triggered VSMCs proliferation with particular emphasis on ERK1/2 signalling pathways. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review.
T2  - Current Pharmaceutical Design
T1  - Insulin, Thrombin, ERK1/2 Kinase and Vascular Smooth Muscle Cells Proliferation
VL  - 16
IS  - 35
SP  - 3895
EP  - 3902
DO  - 10.2174/138161210794454987
ER  - 

@article{
author = "Isenović, Esma R. and Soskić, Sanja S. and Trpković, Andreja and Dobutović, Branislava and Popović, Milan and Gluvić, Zoran and Putniković, Biljana and Marche, Pierre",
year = "2010",
abstract = "Vascular smooth muscle cells (VSMC) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMC allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMC proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Signal transduction pathways in eukaryotic cells integrate diverse extracellular signals, and regulate complex biological responses such as growth, differentiation and death. One group of proline-directed Ser/Thr protein kinases, the mitogen-activated protein kinases (MAPKs), plays a central role in these signalling pathways. Much attention has focused in recent years on subfamilies of MAPKs, the extracellular signal regulated kinases (ERKs). Here we overview the work on ERKs 1 to 2, emphasising when possible their biological activities in VSMC proliferation. It is clear from numerosus studies including our own, that ERK1/ERK2 pathway has an imoprtant role in VSMC proliferation induced by insulin (INS) and thrombin. Despite the physiological and pathophysiological importance of INS and thrombin, possible signal transduction pathways involved in INS and thrombin regulation of VSMCs proliferation remains poorly understood. Thus, this review examines recent findings in signalling mechanisms involved in INS and thrombin-triggered VSMCs proliferation with particular emphasis on ERK1/2 signalling pathways. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review.",
journal = "Current Pharmaceutical Design",
title = "Insulin, Thrombin, ERK1/2 Kinase and Vascular Smooth Muscle Cells Proliferation",
volume = "16",
number = "35",
pages = "3895-3902",
doi = "10.2174/138161210794454987"
}

Isenović, E. R., Soskić, S. S., Trpković, A., Dobutović, B., Popović, M., Gluvić, Z., Putniković, B.,& Marche, P.. (2010). Insulin, Thrombin, ERK1/2 Kinase and Vascular Smooth Muscle Cells Proliferation. in Current Pharmaceutical Design, 16(35), 3895-3902.
https://doi.org/10.2174/138161210794454987

Isenović ER, Soskić SS, Trpković A, Dobutović B, Popović M, Gluvić Z, Putniković B, Marche P. Insulin, Thrombin, ERK1/2 Kinase and Vascular Smooth Muscle Cells Proliferation. in Current Pharmaceutical Design. 2010;16(35):3895-3902.
doi:10.2174/138161210794454987 .

Isenović, Esma R., Soskić, Sanja S., Trpković, Andreja, Dobutović, Branislava, Popović, Milan, Gluvić, Zoran, Putniković, Biljana, Marche, Pierre, "Insulin, Thrombin, ERK1/2 Kinase and Vascular Smooth Muscle Cells Proliferation" in Current Pharmaceutical Design, 16, no. 35 (2010):3895-3902,
https://doi.org/10.2174/138161210794454987 . .

TY  - JOUR
AU  - Isenović, Esma R.
AU  - Kedees, Mamdouh H.
AU  - Haidara, Mohamed A.
AU  - Trpković, Andreja
AU  - Mikhailidis, Dimitri P.
AU  - Marche, Pierre
PY  - 2010
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3984
AB  - It is well recognized that the proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42- and 44-kDa isoforms (ERK1/2)participate in the cellular mitogenic machinery triggered by several VSMCs activators, including insulin (INS) and thrombin (Thr). However, understanding of the intracellular signal transduction pathways involved is incomplete. This review considers the recent findings in INS and Thr signaling mechanisms that modulate the proliferation of VSMCs with particular emphasis on the ERK1/2 signaling pathway, an important mediator of VSMCs hypertrophy and vascular disease. Moreover, because the ERK1/2 pathway have been acknowledged as an important mediator of VSMCs hypertrophy, ERK1/2 is identified as a key target for novel therapeutic interventions to minimize irreversible tissue damage associated with hypertension and atherosclerosis.
T2  - Angiology
T1  - Involvement of ERK1/2 Kinase in Insulin- and Thrombin-Stimulated Vascular Smooth Muscle Cell Proliferation
VL  - 61
IS  - 4
SP  - 357
EP  - 364
DO  - 10.1177/0003319709358693
ER  - 

@article{
author = "Isenović, Esma R. and Kedees, Mamdouh H. and Haidara, Mohamed A. and Trpković, Andreja and Mikhailidis, Dimitri P. and Marche, Pierre",
year = "2010",
abstract = "It is well recognized that the proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42- and 44-kDa isoforms (ERK1/2)participate in the cellular mitogenic machinery triggered by several VSMCs activators, including insulin (INS) and thrombin (Thr). However, understanding of the intracellular signal transduction pathways involved is incomplete. This review considers the recent findings in INS and Thr signaling mechanisms that modulate the proliferation of VSMCs with particular emphasis on the ERK1/2 signaling pathway, an important mediator of VSMCs hypertrophy and vascular disease. Moreover, because the ERK1/2 pathway have been acknowledged as an important mediator of VSMCs hypertrophy, ERK1/2 is identified as a key target for novel therapeutic interventions to minimize irreversible tissue damage associated with hypertension and atherosclerosis.",
journal = "Angiology",
title = "Involvement of ERK1/2 Kinase in Insulin- and Thrombin-Stimulated Vascular Smooth Muscle Cell Proliferation",
volume = "61",
number = "4",
pages = "357-364",
doi = "10.1177/0003319709358693"
}

Isenović, E. R., Kedees, M. H., Haidara, M. A., Trpković, A., Mikhailidis, D. P.,& Marche, P.. (2010). Involvement of ERK1/2 Kinase in Insulin- and Thrombin-Stimulated Vascular Smooth Muscle Cell Proliferation. in Angiology, 61(4), 357-364.
https://doi.org/10.1177/0003319709358693

Isenović ER, Kedees MH, Haidara MA, Trpković A, Mikhailidis DP, Marche P. Involvement of ERK1/2 Kinase in Insulin- and Thrombin-Stimulated Vascular Smooth Muscle Cell Proliferation. in Angiology. 2010;61(4):357-364.
doi:10.1177/0003319709358693 .

Isenović, Esma R., Kedees, Mamdouh H., Haidara, Mohamed A., Trpković, Andreja, Mikhailidis, Dimitri P., Marche, Pierre, "Involvement of ERK1/2 Kinase in Insulin- and Thrombin-Stimulated Vascular Smooth Muscle Cell Proliferation" in Angiology, 61, no. 4 (2010):357-364,
https://doi.org/10.1177/0003319709358693 . .

TY  - JOUR
AU  - Isenović, Esma R.
AU  - Kedees, Mamdouh H.
AU  - Tepavčević, Snežana
AU  - Milosavljević, Tijana
AU  - Korićanac, Goran
AU  - Trpković, Andreja
AU  - Marche, Pierre
PY  - 2009
UR  - http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1871-529X&volume=9&issue=3&spage=172
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7802
AB  - Vascular smooth muscle cells (VSMCs) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMCs allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMCs proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Phosphorylation/dephosphorylation reactions of enzymes belonging to the family of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) play an important role in the transduction of mitogenic signal. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42 and 44 kDa isoforms (ERK1/2) as well as Akt and cytosolic phospholipase 2 (cPLA 2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including insulin (INS). The ability of INS to significantly increase VSMCs proliferation has been demonstrated in several systems, but understanding of the intracellular signal transduction pathways involved is incomplete. Signal transduction pathways involved in regulation of the VSMCs proliferation by INS remains poorly understood. Thus, this review examines recent findings in signaling mechanisms employed by INS in modulating the regulation of proliferation of VSMCs with particular emphasis on PI3K/Akt, cPLA2 and ERK1/2 signaling pathways that have been identified as important mediators of VSMCs hypertrophy and vascular diseases. These findings are critical for understanding the role of INS in vascular biology and hyperinsulinemia.
T2  - Cardiovascular and Hematological Disorders-Drug Targets
T1  - Role of PI3K/AKT, cPLA2 and ERK1/2 Signaling Pathways in Insulin Regulation of Vascular Smooth Muscle Cells Proliferation
VL  - 9
IS  - 3
SP  - 172
EP  - 180
DO  - 10.2174/187152909789007034
ER  - 

@article{
author = "Isenović, Esma R. and Kedees, Mamdouh H. and Tepavčević, Snežana and Milosavljević, Tijana and Korićanac, Goran and Trpković, Andreja and Marche, Pierre",
year = "2009",
abstract = "Vascular smooth muscle cells (VSMCs) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMCs allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMCs proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Phosphorylation/dephosphorylation reactions of enzymes belonging to the family of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) play an important role in the transduction of mitogenic signal. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42 and 44 kDa isoforms (ERK1/2) as well as Akt and cytosolic phospholipase 2 (cPLA 2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including insulin (INS). The ability of INS to significantly increase VSMCs proliferation has been demonstrated in several systems, but understanding of the intracellular signal transduction pathways involved is incomplete. Signal transduction pathways involved in regulation of the VSMCs proliferation by INS remains poorly understood. Thus, this review examines recent findings in signaling mechanisms employed by INS in modulating the regulation of proliferation of VSMCs with particular emphasis on PI3K/Akt, cPLA2 and ERK1/2 signaling pathways that have been identified as important mediators of VSMCs hypertrophy and vascular diseases. These findings are critical for understanding the role of INS in vascular biology and hyperinsulinemia.",
journal = "Cardiovascular and Hematological Disorders-Drug Targets",
title = "Role of PI3K/AKT, cPLA2 and ERK1/2 Signaling Pathways in Insulin Regulation of Vascular Smooth Muscle Cells Proliferation",
volume = "9",
number = "3",
pages = "172-180",
doi = "10.2174/187152909789007034"
}

Isenović, E. R., Kedees, M. H., Tepavčević, S., Milosavljević, T., Korićanac, G., Trpković, A.,& Marche, P.. (2009). Role of PI3K/AKT, cPLA2 and ERK1/2 Signaling Pathways in Insulin Regulation of Vascular Smooth Muscle Cells Proliferation. in Cardiovascular and Hematological Disorders-Drug Targets, 9(3), 172-180.
https://doi.org/10.2174/187152909789007034

Isenović ER, Kedees MH, Tepavčević S, Milosavljević T, Korićanac G, Trpković A, Marche P. Role of PI3K/AKT, cPLA2 and ERK1/2 Signaling Pathways in Insulin Regulation of Vascular Smooth Muscle Cells Proliferation. in Cardiovascular and Hematological Disorders-Drug Targets. 2009;9(3):172-180.
doi:10.2174/187152909789007034 .

Isenović, Esma R., Kedees, Mamdouh H., Tepavčević, Snežana, Milosavljević, Tijana, Korićanac, Goran, Trpković, Andreja, Marche, Pierre, "Role of PI3K/AKT, cPLA2 and ERK1/2 Signaling Pathways in Insulin Regulation of Vascular Smooth Muscle Cells Proliferation" in Cardiovascular and Hematological Disorders-Drug Targets, 9, no. 3 (2009):172-180,
https://doi.org/10.2174/187152909789007034 . .

TY  - JOUR
AU  - Isenović, Esma R.
AU  - Kedees, Mamdouh H.
AU  - Tepavčević, Snežana
AU  - Milosavljević, Tijana
AU  - Korićanac, Goran
AU  - Trpković, Andreja
AU  - Marche, Pierre
PY  - 2009
UR  - http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1871-529X&volume=9&issue=3&spage=172
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7832
AB  - Vascular smooth muscle cells (VSMCs) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMCs allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMCs proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Phosphorylation/dephosphorylation reactions of enzymes belonging to the family of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) play an important role in the transduction of mitogenic signal. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42 and 44 kDa isoforms (ERK1/2) as well as Akt and cytosolic phospholipase 2 (cPLA 2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including insulin (INS). The ability of INS to significantly increase VSMCs proliferation has been demonstrated in several systems, but understanding of the intracellular signal transduction pathways involved is incomplete. Signal transduction pathways involved in regulation of the VSMCs proliferation by INS remains poorly understood. Thus, this review examines recent findings in signaling mechanisms employed by INS in modulating the regulation of proliferation of VSMCs with particular emphasis on PI3K/Akt, cPLA2 and ERK1/2 signaling pathways that have been identified as important mediators of VSMCs hypertrophy and vascular diseases. These findings are critical for understanding the role of INS in vascular biology and hyperinsulinemia.
T2  - Cardiovascular and Hematological Disorders-Drug Targets
T1  - Role of PI3K/AKT, cPLA2 and ERK1/2 Signaling Pathways in Insulin Regulation of Vascular Smooth Muscle Cells Proliferation
VL  - 9
IS  - 3
SP  - 172
EP  - 180
DO  - 10.2174/187152909789007034
ER  - 

@article{
author = "Isenović, Esma R. and Kedees, Mamdouh H. and Tepavčević, Snežana and Milosavljević, Tijana and Korićanac, Goran and Trpković, Andreja and Marche, Pierre",
year = "2009",
abstract = "Vascular smooth muscle cells (VSMCs) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMCs allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMCs proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Phosphorylation/dephosphorylation reactions of enzymes belonging to the family of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) play an important role in the transduction of mitogenic signal. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42 and 44 kDa isoforms (ERK1/2) as well as Akt and cytosolic phospholipase 2 (cPLA 2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including insulin (INS). The ability of INS to significantly increase VSMCs proliferation has been demonstrated in several systems, but understanding of the intracellular signal transduction pathways involved is incomplete. Signal transduction pathways involved in regulation of the VSMCs proliferation by INS remains poorly understood. Thus, this review examines recent findings in signaling mechanisms employed by INS in modulating the regulation of proliferation of VSMCs with particular emphasis on PI3K/Akt, cPLA2 and ERK1/2 signaling pathways that have been identified as important mediators of VSMCs hypertrophy and vascular diseases. These findings are critical for understanding the role of INS in vascular biology and hyperinsulinemia.",
journal = "Cardiovascular and Hematological Disorders-Drug Targets",
title = "Role of PI3K/AKT, cPLA2 and ERK1/2 Signaling Pathways in Insulin Regulation of Vascular Smooth Muscle Cells Proliferation",
volume = "9",
number = "3",
pages = "172-180",
doi = "10.2174/187152909789007034"
}

Isenović, E. R., Kedees, M. H., Tepavčević, S., Milosavljević, T., Korićanac, G., Trpković, A.,& Marche, P.. (2009). Role of PI3K/AKT, cPLA2 and ERK1/2 Signaling Pathways in Insulin Regulation of Vascular Smooth Muscle Cells Proliferation. in Cardiovascular and Hematological Disorders-Drug Targets, 9(3), 172-180.
https://doi.org/10.2174/187152909789007034

Isenović ER, Kedees MH, Tepavčević S, Milosavljević T, Korićanac G, Trpković A, Marche P. Role of PI3K/AKT, cPLA2 and ERK1/2 Signaling Pathways in Insulin Regulation of Vascular Smooth Muscle Cells Proliferation. in Cardiovascular and Hematological Disorders-Drug Targets. 2009;9(3):172-180.
doi:10.2174/187152909789007034 .

Isenović, Esma R., Kedees, Mamdouh H., Tepavčević, Snežana, Milosavljević, Tijana, Korićanac, Goran, Trpković, Andreja, Marche, Pierre, "Role of PI3K/AKT, cPLA2 and ERK1/2 Signaling Pathways in Insulin Regulation of Vascular Smooth Muscle Cells Proliferation" in Cardiovascular and Hematological Disorders-Drug Targets, 9, no. 3 (2009):172-180,
https://doi.org/10.2174/187152909789007034 . .

TY  - JOUR
AU  - Isenović, Esma R.
AU  - Fretaud, Maxence
AU  - Dobutović, Branislava
AU  - Sudar, Emina
AU  - Smiljanić, Katarina
AU  - Zarić, Božidarka
AU  - Trpković, Andreja
AU  - Marche, Pierre
PY  - 2009
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3644
AB  - Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44 mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase (PI3K). In addition, cytosolic phospholipase 2 (cPLA(2)) is linked to VSMCs proliferation. However, the upstream mechanisms responsible for activation of cPLA(2) are not well defined. Therefore, this investigation used primary cultured rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent phosphorylation of cPLA(2) and proliferation induced by INS. Exposure of VSMCs to INS (100 nM) for 10 min increased the phosphorylation of cPLA(2) by 1.5-fold (p LT 0.01), which was blocked by the cPLA(2) inhibitor MAFP (10 mu M; 15 min). Similarly, the PI3K inhibitor LY294002 (10 mu M; 15 min) and ERK1/2 inhibitor PD98059 (20 mu M; 15 min) abolished the INS-mediated increase in cPLA(2) phosphorylation by 59% (p LT 0.001), and by 75% (p LT 0.001), respectively. Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS-stimulated ERK1/2 phosphorylation by 65% (p LT 0.01). Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 85% (p LT 0.001). The effect of INS on VSMCs proliferation was significantly (p LT 0.01) reduced by pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs proliferation via a mechanism involving the PI3K-dependent activation of cPLA(2) and release of arachidonic acid (AA), which activates ERK1/2 and further amplifies cPLA(2) activity. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
T2  - Cell Biology International
T1  - A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells
VL  - 33
IS  - 3
SP  - 386
EP  - 392
DO  - 10.1016/j.cellbi.2009.01.010
ER  - 

@article{
author = "Isenović, Esma R. and Fretaud, Maxence and Dobutović, Branislava and Sudar, Emina and Smiljanić, Katarina and Zarić, Božidarka and Trpković, Andreja and Marche, Pierre",
year = "2009",
abstract = "Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44 mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase (PI3K). In addition, cytosolic phospholipase 2 (cPLA(2)) is linked to VSMCs proliferation. However, the upstream mechanisms responsible for activation of cPLA(2) are not well defined. Therefore, this investigation used primary cultured rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent phosphorylation of cPLA(2) and proliferation induced by INS. Exposure of VSMCs to INS (100 nM) for 10 min increased the phosphorylation of cPLA(2) by 1.5-fold (p LT 0.01), which was blocked by the cPLA(2) inhibitor MAFP (10 mu M; 15 min). Similarly, the PI3K inhibitor LY294002 (10 mu M; 15 min) and ERK1/2 inhibitor PD98059 (20 mu M; 15 min) abolished the INS-mediated increase in cPLA(2) phosphorylation by 59% (p LT 0.001), and by 75% (p LT 0.001), respectively. Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS-stimulated ERK1/2 phosphorylation by 65% (p LT 0.01). Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 85% (p LT 0.001). The effect of INS on VSMCs proliferation was significantly (p LT 0.01) reduced by pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs proliferation via a mechanism involving the PI3K-dependent activation of cPLA(2) and release of arachidonic acid (AA), which activates ERK1/2 and further amplifies cPLA(2) activity. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.",
journal = "Cell Biology International",
title = "A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells",
volume = "33",
number = "3",
pages = "386-392",
doi = "10.1016/j.cellbi.2009.01.010"
}

Isenović, E. R., Fretaud, M., Dobutović, B., Sudar, E., Smiljanić, K., Zarić, B., Trpković, A.,& Marche, P.. (2009). A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells. in Cell Biology International, 33(3), 386-392.
https://doi.org/10.1016/j.cellbi.2009.01.010

Isenović ER, Fretaud M, Dobutović B, Sudar E, Smiljanić K, Zarić B, Trpković A, Marche P. A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells. in Cell Biology International. 2009;33(3):386-392.
doi:10.1016/j.cellbi.2009.01.010 .

Isenović, Esma R., Fretaud, Maxence, Dobutović, Branislava, Sudar, Emina, Smiljanić, Katarina, Zarić, Božidarka, Trpković, Andreja, Marche, Pierre, "A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells" in Cell Biology International, 33, no. 3 (2009):386-392,
https://doi.org/10.1016/j.cellbi.2009.01.010 . .

TY  - JOUR
AU  - Isenović, Esma R.
AU  - Fretaud, M.
AU  - Korićanac, Goran
AU  - Sudar, Emina
AU  - Velebit, Jelena
AU  - Dobutovic, B.
AU  - Marche, Pierre
PY  - 2009
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3718
AB  - This investigation used primary cultured rat vascular smooth muscle cells (VSMCs) to examine the effect of insulin (INS) on proliferation of VSMCs. In this study, we investigated the role of protein kinase B (Akt) and p42/44 mitogen-activated protein kinase (ERK 1/2) signaling pathways in mediating the mitogenic action of INS in VSMCs. Incubation of rat VSMCs with INS (100 nM) for 10 min resulted man increase of Akt phosphorylation by 6-fold (p LT 0.001) and ERK 1/2 phosphorylation by 3-fold (p LT 0.001). Pretreatment for 15 min with 10 mu M of PI3K/Akt inhibitor LY294002 or with 20 mu M PD98059, inhibitor of ERK 1/2, significantly reduced INS-stimulated Akt and ERK 1/2 phosphorylation by 76 and 75%, respectively. Prolonged treatment of VSMCs with INS for 24 h did not have an effect on either Akt or ERK 1/2 phosphorylation. Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 87% (p LT 0.001.) The effect of INS on VSMCs proliferation was significantly reduced by 68% by pretreatment with LY294002 (p GT 0.01) and by 71% (p GT 0.01) by pretreatment with PD98059. These results indicate that INS acts through Akt and ERK 1/2 signaling pathways to Up-regulate proliferation of VSMCs.
T2  - Experimental and Clinical Endocrinology and Diabetes
T1  - Insulin Regulation of Proliferation Involves Activation of AKT and ERK 1/2 Signaling Pathways in Vascular Smooth Muscle Cells
VL  - 117
IS  - 5
SP  - 214
EP  - 219
DO  - 10.1055/s-0028-1085470
ER  - 

@article{
author = "Isenović, Esma R. and Fretaud, M. and Korićanac, Goran and Sudar, Emina and Velebit, Jelena and Dobutovic, B. and Marche, Pierre",
year = "2009",
abstract = "This investigation used primary cultured rat vascular smooth muscle cells (VSMCs) to examine the effect of insulin (INS) on proliferation of VSMCs. In this study, we investigated the role of protein kinase B (Akt) and p42/44 mitogen-activated protein kinase (ERK 1/2) signaling pathways in mediating the mitogenic action of INS in VSMCs. Incubation of rat VSMCs with INS (100 nM) for 10 min resulted man increase of Akt phosphorylation by 6-fold (p LT 0.001) and ERK 1/2 phosphorylation by 3-fold (p LT 0.001). Pretreatment for 15 min with 10 mu M of PI3K/Akt inhibitor LY294002 or with 20 mu M PD98059, inhibitor of ERK 1/2, significantly reduced INS-stimulated Akt and ERK 1/2 phosphorylation by 76 and 75%, respectively. Prolonged treatment of VSMCs with INS for 24 h did not have an effect on either Akt or ERK 1/2 phosphorylation. Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 87% (p LT 0.001.) The effect of INS on VSMCs proliferation was significantly reduced by 68% by pretreatment with LY294002 (p GT 0.01) and by 71% (p GT 0.01) by pretreatment with PD98059. These results indicate that INS acts through Akt and ERK 1/2 signaling pathways to Up-regulate proliferation of VSMCs.",
journal = "Experimental and Clinical Endocrinology and Diabetes",
title = "Insulin Regulation of Proliferation Involves Activation of AKT and ERK 1/2 Signaling Pathways in Vascular Smooth Muscle Cells",
volume = "117",
number = "5",
pages = "214-219",
doi = "10.1055/s-0028-1085470"
}

Isenović, E. R., Fretaud, M., Korićanac, G., Sudar, E., Velebit, J., Dobutovic, B.,& Marche, P.. (2009). Insulin Regulation of Proliferation Involves Activation of AKT and ERK 1/2 Signaling Pathways in Vascular Smooth Muscle Cells. in Experimental and Clinical Endocrinology and Diabetes, 117(5), 214-219.
https://doi.org/10.1055/s-0028-1085470

Isenović ER, Fretaud M, Korićanac G, Sudar E, Velebit J, Dobutovic B, Marche P. Insulin Regulation of Proliferation Involves Activation of AKT and ERK 1/2 Signaling Pathways in Vascular Smooth Muscle Cells. in Experimental and Clinical Endocrinology and Diabetes. 2009;117(5):214-219.
doi:10.1055/s-0028-1085470 .

Isenović, Esma R., Fretaud, M., Korićanac, Goran, Sudar, Emina, Velebit, Jelena, Dobutovic, B., Marche, Pierre, "Insulin Regulation of Proliferation Involves Activation of AKT and ERK 1/2 Signaling Pathways in Vascular Smooth Muscle Cells" in Experimental and Clinical Endocrinology and Diabetes, 117, no. 5 (2009):214-219,
https://doi.org/10.1055/s-0028-1085470 . .

TY  - JOUR
AU  - Isenović, Esma R.
AU  - Trpković, Andreja
AU  - Žakula, Zorica
AU  - Korićanac, Goran
AU  - Marche, Pierre
PY  - 2008
UR  - http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1573-4021&volume=4&issue=3&spage=190
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7803
AB  - It is well recognized that the proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. It is generally considered that the phosphorylation/dephosphorylation reactions of a variety of enzymes belonging to the family of mitogen-activated protein kinases (MAPKs) play an important role in the transduction of mitogenic signal. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42 and 44 kDa isoforms (ERK1/2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including thrombin. ERK1/2 activation by G-protein-coupled receptors (GPCRs) has been shown to be Ca2--dependent and to require the transactivation of epidermal growth factor receptor (EGFR). In addition, it is generally admitted that variations of the intracellular Ca2- concentration ([Ca2-] i) play an important role in the transduction of mitogenic signal. Recently, we have shown that in thrombin-stimulated VSMCs, EGFR-independent activation of ERK1/2 activation could occur when agonist-induced ([Ca2-] i) elevation was reduced. This review examines recent findings in ERK1/2 signaling pathway that have been identified as critically important mediator of VSMCs hypertrophy and vascular diseases. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review.
T2  - Current Hypertension Reviews
T1  - Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy
VL  - 4
IS  - 3
SP  - 190
EP  - 196
DO  - 10.2174/157340208785132590
ER  - 

@article{
author = "Isenović, Esma R. and Trpković, Andreja and Žakula, Zorica and Korićanac, Goran and Marche, Pierre",
year = "2008",
abstract = "It is well recognized that the proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. It is generally considered that the phosphorylation/dephosphorylation reactions of a variety of enzymes belonging to the family of mitogen-activated protein kinases (MAPKs) play an important role in the transduction of mitogenic signal. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42 and 44 kDa isoforms (ERK1/2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including thrombin. ERK1/2 activation by G-protein-coupled receptors (GPCRs) has been shown to be Ca2--dependent and to require the transactivation of epidermal growth factor receptor (EGFR). In addition, it is generally admitted that variations of the intracellular Ca2- concentration ([Ca2-] i) play an important role in the transduction of mitogenic signal. Recently, we have shown that in thrombin-stimulated VSMCs, EGFR-independent activation of ERK1/2 activation could occur when agonist-induced ([Ca2-] i) elevation was reduced. This review examines recent findings in ERK1/2 signaling pathway that have been identified as critically important mediator of VSMCs hypertrophy and vascular diseases. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review.",
journal = "Current Hypertension Reviews",
title = "Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy",
volume = "4",
number = "3",
pages = "190-196",
doi = "10.2174/157340208785132590"
}

Isenović, E. R., Trpković, A., Žakula, Z., Korićanac, G.,& Marche, P.. (2008). Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy. in Current Hypertension Reviews, 4(3), 190-196.
https://doi.org/10.2174/157340208785132590

Isenović ER, Trpković A, Žakula Z, Korićanac G, Marche P. Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy. in Current Hypertension Reviews. 2008;4(3):190-196.
doi:10.2174/157340208785132590 .

Isenović, Esma R., Trpković, Andreja, Žakula, Zorica, Korićanac, Goran, Marche, Pierre, "Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy" in Current Hypertension Reviews, 4, no. 3 (2008):190-196,
https://doi.org/10.2174/157340208785132590 . .

TY  - JOUR
AU  - Isenović, Esma R.
AU  - Trpković, Andreja
AU  - Žakula, Zorica
AU  - Korićanac, Goran
AU  - Marche, Pierre
PY  - 2008
UR  - http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1573-4021&volume=4&issue=3&spage=190
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7837
AB  - It is well recognized that the proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. It is generally considered that the phosphorylation/dephosphorylation reactions of a variety of enzymes belonging to the family of mitogen-activated protein kinases (MAPKs) play an important role in the transduction of mitogenic signal. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42 and 44 kDa isoforms (ERK1/2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including thrombin. ERK1/2 activation by G-protein-coupled receptors (GPCRs) has been shown to be Ca2--dependent and to require the transactivation of epidermal growth factor receptor (EGFR). In addition, it is generally admitted that variations of the intracellular Ca2- concentration ([Ca2-] i) play an important role in the transduction of mitogenic signal. Recently, we have shown that in thrombin-stimulated VSMCs, EGFR-independent activation of ERK1/2 activation could occur when agonist-induced ([Ca2-] i) elevation was reduced. This review examines recent findings in ERK1/2 signaling pathway that have been identified as critically important mediator of VSMCs hypertrophy and vascular diseases. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review. © 2008 Bentham Science Publishers Ltd.
T2  - Current Hypertension Reviews
T1  - Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy
VL  - 4
IS  - 3
SP  - 190
EP  - 196
DO  - 10.2174/157340208785132590
ER  - 

@article{
author = "Isenović, Esma R. and Trpković, Andreja and Žakula, Zorica and Korićanac, Goran and Marche, Pierre",
year = "2008",
abstract = "It is well recognized that the proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. It is generally considered that the phosphorylation/dephosphorylation reactions of a variety of enzymes belonging to the family of mitogen-activated protein kinases (MAPKs) play an important role in the transduction of mitogenic signal. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42 and 44 kDa isoforms (ERK1/2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including thrombin. ERK1/2 activation by G-protein-coupled receptors (GPCRs) has been shown to be Ca2--dependent and to require the transactivation of epidermal growth factor receptor (EGFR). In addition, it is generally admitted that variations of the intracellular Ca2- concentration ([Ca2-] i) play an important role in the transduction of mitogenic signal. Recently, we have shown that in thrombin-stimulated VSMCs, EGFR-independent activation of ERK1/2 activation could occur when agonist-induced ([Ca2-] i) elevation was reduced. This review examines recent findings in ERK1/2 signaling pathway that have been identified as critically important mediator of VSMCs hypertrophy and vascular diseases. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review. © 2008 Bentham Science Publishers Ltd.",
journal = "Current Hypertension Reviews",
title = "Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy",
volume = "4",
number = "3",
pages = "190-196",
doi = "10.2174/157340208785132590"
}

Isenović, E. R., Trpković, A., Žakula, Z., Korićanac, G.,& Marche, P.. (2008). Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy. in Current Hypertension Reviews, 4(3), 190-196.
https://doi.org/10.2174/157340208785132590

Isenović ER, Trpković A, Žakula Z, Korićanac G, Marche P. Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy. in Current Hypertension Reviews. 2008;4(3):190-196.
doi:10.2174/157340208785132590 .

Isenović, Esma R., Trpković, Andreja, Žakula, Zorica, Korićanac, Goran, Marche, Pierre, "Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy" in Current Hypertension Reviews, 4, no. 3 (2008):190-196,
https://doi.org/10.2174/157340208785132590 . .