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  - CHAP
AU  - Sudar, Emina
AU  - Soskić, Sanja S.
AU  - Zarić, Božidarka
AU  - Rašić-Milutinović, Zorica
AU  - Smiljanić, Katarina
AU  - Radak, Đorđe J.
AU  - Mikhailidis, Dimitri P.
AU  - Rizzo, Manfredi
AU  - Isenović, Esma R.
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8685
AB  - Cardiovascular disease (CVD) is common cause of death in humans and its major underlying pathology is atherosclerosis. Atherosclerosis is a chronic inflammatory disease that predisposes to coronary artery disease (CAD), stroke and peripheral arterial disease, responsible for most of the cardiovascular morbidity and mortality. This inflammatory process, triggered by the presence of lipids in the vascular wall, and encompasses a complex interaction among inflammatory cells, vascular elements, and lipoproteins through the expression of several adhesion molecules and cytokines. Obesity is a risk factor for CVD but this association is not fully understood. Altered levels of obesity related peptides such as ghrelin may play an important role in this pathophysiology. Recent evidence indicates that ghrelin features several cardiovascular activities, including increased myocardial contractility, vasodilatation and protection from myocardial infarction. Recent data demonstrate that ghrelin can influence important key events in atherogenesis and thus they may play a role in atherosclerosis. In this review we present the latest data from recent animal and clinical studies which focus on a novel approach to ghrelin as a potential therapeutic agent in the treatment of a complex disease like atherosclerosis. Thus, ghrelin may become a new therapeutic target for the treatment of CVD. Further studies are necessary to investigate the potential mechanisms involved in the effects of ghrelin on the cardiovascular system.
T2  - Ghrelin: Production, Action Mechanisms and Physiological Effects
T1  - Ghrelin, obesity and atherosclerosis
SP  - 111
EP  - 126
UR  - https://hdl.handle.net/21.15107/rcub_vinar_8685
ER  - 

@inbook{
author = "Sudar, Emina and Soskić, Sanja S. and Zarić, Božidarka and Rašić-Milutinović, Zorica and Smiljanić, Katarina and Radak, Đorđe J. and Mikhailidis, Dimitri P. and Rizzo, Manfredi and Isenović, Esma R.",
year = "2012",
abstract = "Cardiovascular disease (CVD) is common cause of death in humans and its major underlying pathology is atherosclerosis. Atherosclerosis is a chronic inflammatory disease that predisposes to coronary artery disease (CAD), stroke and peripheral arterial disease, responsible for most of the cardiovascular morbidity and mortality. This inflammatory process, triggered by the presence of lipids in the vascular wall, and encompasses a complex interaction among inflammatory cells, vascular elements, and lipoproteins through the expression of several adhesion molecules and cytokines. Obesity is a risk factor for CVD but this association is not fully understood. Altered levels of obesity related peptides such as ghrelin may play an important role in this pathophysiology. Recent evidence indicates that ghrelin features several cardiovascular activities, including increased myocardial contractility, vasodilatation and protection from myocardial infarction. Recent data demonstrate that ghrelin can influence important key events in atherogenesis and thus they may play a role in atherosclerosis. In this review we present the latest data from recent animal and clinical studies which focus on a novel approach to ghrelin as a potential therapeutic agent in the treatment of a complex disease like atherosclerosis. Thus, ghrelin may become a new therapeutic target for the treatment of CVD. Further studies are necessary to investigate the potential mechanisms involved in the effects of ghrelin on the cardiovascular system.",
journal = "Ghrelin: Production, Action Mechanisms and Physiological Effects",
booktitle = "Ghrelin, obesity and atherosclerosis",
pages = "111-126",
url = "https://hdl.handle.net/21.15107/rcub_vinar_8685"
}

Sudar, E., Soskić, S. S., Zarić, B., Rašić-Milutinović, Z., Smiljanić, K., Radak, Đ. J., Mikhailidis, D. P., Rizzo, M.,& Isenović, E. R.. (2012). Ghrelin, obesity and atherosclerosis. in Ghrelin: Production, Action Mechanisms and Physiological Effects, 111-126.
https://hdl.handle.net/21.15107/rcub_vinar_8685

Sudar E, Soskić SS, Zarić B, Rašić-Milutinović Z, Smiljanić K, Radak ĐJ, Mikhailidis DP, Rizzo M, Isenović ER. Ghrelin, obesity and atherosclerosis. in Ghrelin: Production, Action Mechanisms and Physiological Effects. 2012;:111-126.
https://hdl.handle.net/21.15107/rcub_vinar_8685 .

Sudar, Emina, Soskić, Sanja S., Zarić, Božidarka, Rašić-Milutinović, Zorica, Smiljanić, Katarina, Radak, Đorđe J., Mikhailidis, Dimitri P., Rizzo, Manfredi, Isenović, Esma R., "Ghrelin, obesity and atherosclerosis" in Ghrelin: Production, Action Mechanisms and Physiological Effects (2012):111-126,
https://hdl.handle.net/21.15107/rcub_vinar_8685 .

TY  - JOUR
AU  - Smiljanić, Katarina
AU  - Zafirović, Sonja
AU  - Obradović, Milan M.
AU  - Gluvić, Zoran
AU  - Stokić, Edita
AU  - Putniković, Biljana
AU  - Isenović, Esma R.
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10324
AB  - Glatke mišićne ćelije krvnih sudova (VSMCs) su od vitalnog značaja, kako za strukturu tako i za funkcionisanje i dinamiku krvnih sudova. Proliferacija i abnormalna akumulacija VSMCs su među ključnim događajima u nastanku raznih vaskularnih oboljenja, uključujući aterosklerozu i hipertenziju. Kardiovaskularne bolesti su vodeći uzrok smrtnosti ljudske populacije u čijoj osnovi u najvećoj meri dominira ateroskleroza kao patološka komponenta. Ateroskleroza jedan je od glavnih uzroka infarkta miokarda, moždanog udara i perifernih vaskularnih bolesti, koji čine približno polovinu svih smrtnih slučajeva u razvijenim zemljama. Ona uključuje orkestrirane procese endotelijalne disfunkcije, inflamacije, proliferacije VSMCs i reorganizaciju ekstracelularnog matriksa. Dediferencijacija i proliferacija VSMCs predstavljaju ključne događaje u nastanku aterosklerotskih lezija, postangioplastične restenoze i odbacivanja kalema pri bajpasu krvnih sudova. Trombin je moćni modulator mnogih procesa kao što su regulisanje tonusa i propustljivosti krvnog suda, migracije i proliferacije VSMCs, privlačenja monocita u aterosklerotske lezije i raznih proinflamatornih markera, a sve ovo, takođe, doprinosi progresiji kardiovaskularnih oboljenja.
AB  - Vascular smooth muscle cells (VSMCs) are vital to the structure, functioning and dynamics of blood vessels. Proliferation and abnormal accumulation of VSMCs are among the key events in the development of various vascular diseases including atherosclerosis and hypertension. Cardiovascular diseases are the leading cause of mortality in human population which is based largely dominated by atherosclerosis as a pathological component. Atherosclerosis is a major cause of myocardial infarction, stroke and peripheral vascular disease, which constitute approximately half of all deaths in developed countries. It involves orchestrated processes of endothelial dysfunction, inflammation, proliferation of VSMCs and extracellular matrix reorganization. Dedifferentiation and proliferation of VSMCs is a key event in the development of atherosclerotic lesions, postangioplastic restenosis and rejection of the bypass graft vessels. Thrombin is a potent modulator of many processes such as regulation of muscle tone and permeability of the blood vessel, migration and proliferation of VSMCs, attracting monocytes into atherosclerotic lesions and a variety of inflammatory markers, and all this also contributes to the progression of cardiovascular disease.
T2  - Medicinska istraživanja
T1  - Uloga trombina u proliferaciji glatkih mišićnih ćelija krvnih sudova (VSMCs) i aterosklerozi
T1  - The role of thrombin in the proliferation of vascular smooth muscle cells (VSMCs) and atherosclerosis
VL  - 46
IS  - 2
SP  - 44
EP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_vinar_10324
ER  - 

@article{
author = "Smiljanić, Katarina and Zafirović, Sonja and Obradović, Milan M. and Gluvić, Zoran and Stokić, Edita and Putniković, Biljana and Isenović, Esma R.",
year = "2012",
abstract = "Glatke mišićne ćelije krvnih sudova (VSMCs) su od vitalnog značaja, kako za strukturu tako i za funkcionisanje i dinamiku krvnih sudova. Proliferacija i abnormalna akumulacija VSMCs su među ključnim događajima u nastanku raznih vaskularnih oboljenja, uključujući aterosklerozu i hipertenziju. Kardiovaskularne bolesti su vodeći uzrok smrtnosti ljudske populacije u čijoj osnovi u najvećoj meri dominira ateroskleroza kao patološka komponenta. Ateroskleroza jedan je od glavnih uzroka infarkta miokarda, moždanog udara i perifernih vaskularnih bolesti, koji čine približno polovinu svih smrtnih slučajeva u razvijenim zemljama. Ona uključuje orkestrirane procese endotelijalne disfunkcije, inflamacije, proliferacije VSMCs i reorganizaciju ekstracelularnog matriksa. Dediferencijacija i proliferacija VSMCs predstavljaju ključne događaje u nastanku aterosklerotskih lezija, postangioplastične restenoze i odbacivanja kalema pri bajpasu krvnih sudova. Trombin je moćni modulator mnogih procesa kao što su regulisanje tonusa i propustljivosti krvnog suda, migracije i proliferacije VSMCs, privlačenja monocita u aterosklerotske lezije i raznih proinflamatornih markera, a sve ovo, takođe, doprinosi progresiji kardiovaskularnih oboljenja., Vascular smooth muscle cells (VSMCs) are vital to the structure, functioning and dynamics of blood vessels. Proliferation and abnormal accumulation of VSMCs are among the key events in the development of various vascular diseases including atherosclerosis and hypertension. Cardiovascular diseases are the leading cause of mortality in human population which is based largely dominated by atherosclerosis as a pathological component. Atherosclerosis is a major cause of myocardial infarction, stroke and peripheral vascular disease, which constitute approximately half of all deaths in developed countries. It involves orchestrated processes of endothelial dysfunction, inflammation, proliferation of VSMCs and extracellular matrix reorganization. Dedifferentiation and proliferation of VSMCs is a key event in the development of atherosclerotic lesions, postangioplastic restenosis and rejection of the bypass graft vessels. Thrombin is a potent modulator of many processes such as regulation of muscle tone and permeability of the blood vessel, migration and proliferation of VSMCs, attracting monocytes into atherosclerotic lesions and a variety of inflammatory markers, and all this also contributes to the progression of cardiovascular disease.",
journal = "Medicinska istraživanja",
title = "Uloga trombina u proliferaciji glatkih mišićnih ćelija krvnih sudova (VSMCs) i aterosklerozi, The role of thrombin in the proliferation of vascular smooth muscle cells (VSMCs) and atherosclerosis",
volume = "46",
number = "2",
pages = "44-53",
url = "https://hdl.handle.net/21.15107/rcub_vinar_10324"
}

Smiljanić, K., Zafirović, S., Obradović, M. M., Gluvić, Z., Stokić, E., Putniković, B.,& Isenović, E. R.. (2012). Uloga trombina u proliferaciji glatkih mišićnih ćelija krvnih sudova (VSMCs) i aterosklerozi. in Medicinska istraživanja, 46(2), 44-53.
https://hdl.handle.net/21.15107/rcub_vinar_10324

Smiljanić K, Zafirović S, Obradović MM, Gluvić Z, Stokić E, Putniković B, Isenović ER. Uloga trombina u proliferaciji glatkih mišićnih ćelija krvnih sudova (VSMCs) i aterosklerozi. in Medicinska istraživanja. 2012;46(2):44-53.
https://hdl.handle.net/21.15107/rcub_vinar_10324 .

Smiljanić, Katarina, Zafirović, Sonja, Obradović, Milan M., Gluvić, Zoran, Stokić, Edita, Putniković, Biljana, Isenović, Esma R., "Uloga trombina u proliferaciji glatkih mišićnih ćelija krvnih sudova (VSMCs) i aterosklerozi" in Medicinska istraživanja, 46, no. 2 (2012):44-53,
https://hdl.handle.net/21.15107/rcub_vinar_10324 .

TY  - JOUR
AU  - Popović, Milan
AU  - Smiljanić, Katarina
AU  - Dobutović, Branislava
AU  - Syrovets, Tatiana
AU  - Simmet, Thomas
AU  - Isenović, Esma R.
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4578
AB  - Vascular endothelium is a key regulator of homeostasis. In physiological conditions it mediates vascular dilatation, prevents platelet adhesion, and inhibits thrombin generation. However, endothelial dysfunction caused by physical injury of the vascular wall, for example during balloon angioplasty, acute or chronic inflammation, such as in atherothrombosis, creates a proinflammatory environment which supports leukocyte transmigration toward inflammatory sites. At the same time, the dysfunction promotes thrombin generation, fibrin deposition, and coagulation. The serine protease thrombin plays a pivotal role in the coagulation cascade. However, thrombin is not only the key effector of coagulation cascade; it also plays a significant role in inflammatory diseases. It shows an array of effects on endothelial cells, vascular smooth muscle cells, monocytes, and platelets, all of which participate in the vascular pathophysiology such as atherothrombosis. Therefore, thrombin can be considered as an important modulatory molecule of vascular homeostasis. This review summarizes the existing evidence on the role of thrombin in vascular inflammation.
T2  - Molecular and Cellular Biochemistry
T1  - Thrombin and vascular inflammation
VL  - 359
IS  - 1-2
SP  - 301
EP  - 313
DO  - 10.1007/s11010-011-1024-x
ER  - 

@article{
author = "Popović, Milan and Smiljanić, Katarina and Dobutović, Branislava and Syrovets, Tatiana and Simmet, Thomas and Isenović, Esma R.",
year = "2012",
abstract = "Vascular endothelium is a key regulator of homeostasis. In physiological conditions it mediates vascular dilatation, prevents platelet adhesion, and inhibits thrombin generation. However, endothelial dysfunction caused by physical injury of the vascular wall, for example during balloon angioplasty, acute or chronic inflammation, such as in atherothrombosis, creates a proinflammatory environment which supports leukocyte transmigration toward inflammatory sites. At the same time, the dysfunction promotes thrombin generation, fibrin deposition, and coagulation. The serine protease thrombin plays a pivotal role in the coagulation cascade. However, thrombin is not only the key effector of coagulation cascade; it also plays a significant role in inflammatory diseases. It shows an array of effects on endothelial cells, vascular smooth muscle cells, monocytes, and platelets, all of which participate in the vascular pathophysiology such as atherothrombosis. Therefore, thrombin can be considered as an important modulatory molecule of vascular homeostasis. This review summarizes the existing evidence on the role of thrombin in vascular inflammation.",
journal = "Molecular and Cellular Biochemistry",
title = "Thrombin and vascular inflammation",
volume = "359",
number = "1-2",
pages = "301-313",
doi = "10.1007/s11010-011-1024-x"
}

Popović, M., Smiljanić, K., Dobutović, B., Syrovets, T., Simmet, T.,& Isenović, E. R.. (2012). Thrombin and vascular inflammation. in Molecular and Cellular Biochemistry, 359(1-2), 301-313.
https://doi.org/10.1007/s11010-011-1024-x

Popović M, Smiljanić K, Dobutović B, Syrovets T, Simmet T, Isenović ER. Thrombin and vascular inflammation. in Molecular and Cellular Biochemistry. 2012;359(1-2):301-313.
doi:10.1007/s11010-011-1024-x .

Popović, Milan, Smiljanić, Katarina, Dobutović, Branislava, Syrovets, Tatiana, Simmet, Thomas, Isenović, Esma R., "Thrombin and vascular inflammation" in Molecular and Cellular Biochemistry, 359, no. 1-2 (2012):301-313,
https://doi.org/10.1007/s11010-011-1024-x . .

TY  - JOUR
AU  - Popović, Milan
AU  - Smiljanić, Katarina
AU  - Dobutović, Branislava
AU  - Syrovets, Tatiana
AU  - Simmet, Thomas
AU  - Isenović, Esma R.
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4670
AB  - Vascular endothelium, as a key regulator of hemostasis, mediates vascular dilatation, prevents platelet adhesion, and inhibits thrombin generation. Endothelial dysfunction caused by acute or chronic inflammation, such as in atherosclerosis, creates a proinflammatory environment which supports leukocyte transmigration toward inflammatory sites, and at the same time promotes coagulation, thrombin generation, and fibrin deposition in an attempt to close the wound. Life-long persistent infection with human cytomegalovirus (HCMV) has been associated with atherosclerosis. In vivo studies have revealed that HCMV infection of the vessel wall affects various cells including monocytes/macrophages, smooth muscle cells (SMCs) and endothelial cells (ECs). HCMV-infected SMCs within vascular lesions display enhanced proliferation and impaired apoptosis, which contribute to intima-media thickening, plaque formation and restenosis. Monocytes play a central role in the process of viral dissemination, whereas ECs may represent a viral reservoir, maintaining persistent infection in HCMV-infected atherosclerotic patients following the primary infection. Persistent infection leads to dysfunction of ECs and activates proinflammatory signaling involving nuclear factor kappa B, specificity protein 1, and phosphatidylinositol 3-kinase, as well as expression of platelet-derived growth factor receptor. Activation of these pathways promotes enhanced proliferation and migration of monocytes and SMCs into the intima of the vascular wall as well as lipid accumulation and expansion of the atherosclerotic lesion. Moreover, HCMV infection induces enhanced expression of endothelial adhesion molecules and modifies the proteolytic balance in monocytes and macrophages. As a consequence, infected endothelium recruits naive monocytes from the blood stream, and the concomitant interaction between infected ECs and monocytes enables virus transfer to migrating monocytes. Endothelial damage promotes thrombin generation linking inflammation and coagulation. HCMV, in turn, enhances the thrombin generation. The virus carries on its surface the molecular machinery necessary to initiate thrombin generation, and in addition, may interact with the prothrombinase protein complex thereby facilitating thrombin generation. Thus, infection of endothelium may significantly increase the production of thrombin. This might not only contribute to thrombosis in patients with atherosclerosis, but might also induce thrombin-dependent proinflammatory cell activation. This review summarizes the existing evidence on the role of HCMV in vascular inflammation.
T2  - Journal of Thrombosis and Thrombolysis
T1  - Human cytomegalovirus infection and atherothrombosis
VL  - 33
IS  - 2
SP  - 160
EP  - 172
DO  - 10.1007/s11239-011-0662-x
ER  - 

@article{
author = "Popović, Milan and Smiljanić, Katarina and Dobutović, Branislava and Syrovets, Tatiana and Simmet, Thomas and Isenović, Esma R.",
year = "2012",
abstract = "Vascular endothelium, as a key regulator of hemostasis, mediates vascular dilatation, prevents platelet adhesion, and inhibits thrombin generation. Endothelial dysfunction caused by acute or chronic inflammation, such as in atherosclerosis, creates a proinflammatory environment which supports leukocyte transmigration toward inflammatory sites, and at the same time promotes coagulation, thrombin generation, and fibrin deposition in an attempt to close the wound. Life-long persistent infection with human cytomegalovirus (HCMV) has been associated with atherosclerosis. In vivo studies have revealed that HCMV infection of the vessel wall affects various cells including monocytes/macrophages, smooth muscle cells (SMCs) and endothelial cells (ECs). HCMV-infected SMCs within vascular lesions display enhanced proliferation and impaired apoptosis, which contribute to intima-media thickening, plaque formation and restenosis. Monocytes play a central role in the process of viral dissemination, whereas ECs may represent a viral reservoir, maintaining persistent infection in HCMV-infected atherosclerotic patients following the primary infection. Persistent infection leads to dysfunction of ECs and activates proinflammatory signaling involving nuclear factor kappa B, specificity protein 1, and phosphatidylinositol 3-kinase, as well as expression of platelet-derived growth factor receptor. Activation of these pathways promotes enhanced proliferation and migration of monocytes and SMCs into the intima of the vascular wall as well as lipid accumulation and expansion of the atherosclerotic lesion. Moreover, HCMV infection induces enhanced expression of endothelial adhesion molecules and modifies the proteolytic balance in monocytes and macrophages. As a consequence, infected endothelium recruits naive monocytes from the blood stream, and the concomitant interaction between infected ECs and monocytes enables virus transfer to migrating monocytes. Endothelial damage promotes thrombin generation linking inflammation and coagulation. HCMV, in turn, enhances the thrombin generation. The virus carries on its surface the molecular machinery necessary to initiate thrombin generation, and in addition, may interact with the prothrombinase protein complex thereby facilitating thrombin generation. Thus, infection of endothelium may significantly increase the production of thrombin. This might not only contribute to thrombosis in patients with atherosclerosis, but might also induce thrombin-dependent proinflammatory cell activation. This review summarizes the existing evidence on the role of HCMV in vascular inflammation.",
journal = "Journal of Thrombosis and Thrombolysis",
title = "Human cytomegalovirus infection and atherothrombosis",
volume = "33",
number = "2",
pages = "160-172",
doi = "10.1007/s11239-011-0662-x"
}

Popović, M., Smiljanić, K., Dobutović, B., Syrovets, T., Simmet, T.,& Isenović, E. R.. (2012). Human cytomegalovirus infection and atherothrombosis. in Journal of Thrombosis and Thrombolysis, 33(2), 160-172.
https://doi.org/10.1007/s11239-011-0662-x

Popović M, Smiljanić K, Dobutović B, Syrovets T, Simmet T, Isenović ER. Human cytomegalovirus infection and atherothrombosis. in Journal of Thrombosis and Thrombolysis. 2012;33(2):160-172.
doi:10.1007/s11239-011-0662-x .

Popović, Milan, Smiljanić, Katarina, Dobutović, Branislava, Syrovets, Tatiana, Simmet, Thomas, Isenović, Esma R., "Human cytomegalovirus infection and atherothrombosis" in Journal of Thrombosis and Thrombolysis, 33, no. 2 (2012):160-172,
https://doi.org/10.1007/s11239-011-0662-x . .

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  - Haidara, Mohamed A.
AU  - Mikhailidis, Dimitri P.
AU  - Yassin, Hanaa Z.
AU  - Dobutović, Branislava
AU  - Smiljanić, Katarina
AU  - Soskić, Sanja S.
AU  - Mousa, Shaker A.
AU  - Rizzo, Manfredi
AU  - Isenović, Esma R.
PY  - 2011
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4662
AB  - The metabolic syndrome (MetS) is common, and its associated risk burdens of diabetes and cardiovascular disease (CVD) are a major public health problem. The hypothesis that main constituent parameters of the MetS share common pathophysiologic mechanisms provides a conceptual framework for the future research. Exercise and weight loss can prevent insulin resistance and reduce the risk of diseases associated with the MetS. Interrupting intracellular and extracellular reactive oxygen species (ROS) overproduction could also contribute to normalizing the activation of metabolic pathways leading to the onset of diabetes, endothelial dysfunction, and cardiovascular (CV) complications. On the other hand, it is difficult to counteract the development of CV complications by using conventional antioxidants. Indeed, interest has focused on strategies that enhance the removal of ROS using either antioxidants or drugs that enhance endogenous antioxidant defense. Although these strategies have been effective in laboratory experiments, several clinical trials have shown that they do not reduce CV events, and in some cases antioxidants have actually worsened the outcome. More research is needed in this field.
T2  - Current Pharmaceutical Design
T1  - Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome
VL  - 17
IS  - 33
SP  - 3699
EP  - 3712
DO  - 10.2174/138161211798220882
ER  - 

@article{
author = "Haidara, Mohamed A. and Mikhailidis, Dimitri P. and Yassin, Hanaa Z. and Dobutović, Branislava and Smiljanić, Katarina and Soskić, Sanja S. and Mousa, Shaker A. and Rizzo, Manfredi and Isenović, Esma R.",
year = "2011",
abstract = "The metabolic syndrome (MetS) is common, and its associated risk burdens of diabetes and cardiovascular disease (CVD) are a major public health problem. The hypothesis that main constituent parameters of the MetS share common pathophysiologic mechanisms provides a conceptual framework for the future research. Exercise and weight loss can prevent insulin resistance and reduce the risk of diseases associated with the MetS. Interrupting intracellular and extracellular reactive oxygen species (ROS) overproduction could also contribute to normalizing the activation of metabolic pathways leading to the onset of diabetes, endothelial dysfunction, and cardiovascular (CV) complications. On the other hand, it is difficult to counteract the development of CV complications by using conventional antioxidants. Indeed, interest has focused on strategies that enhance the removal of ROS using either antioxidants or drugs that enhance endogenous antioxidant defense. Although these strategies have been effective in laboratory experiments, several clinical trials have shown that they do not reduce CV events, and in some cases antioxidants have actually worsened the outcome. More research is needed in this field.",
journal = "Current Pharmaceutical Design",
title = "Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome",
volume = "17",
number = "33",
pages = "3699-3712",
doi = "10.2174/138161211798220882"
}

Haidara, M. A., Mikhailidis, D. P., Yassin, H. Z., Dobutović, B., Smiljanić, K., Soskić, S. S., Mousa, S. A., Rizzo, M.,& Isenović, E. R.. (2011). Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome. in Current Pharmaceutical Design, 17(33), 3699-3712.
https://doi.org/10.2174/138161211798220882

Haidara MA, Mikhailidis DP, Yassin HZ, Dobutović B, Smiljanić K, Soskić SS, Mousa SA, Rizzo M, Isenović ER. Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome. in Current Pharmaceutical Design. 2011;17(33):3699-3712.
doi:10.2174/138161211798220882 .

Haidara, Mohamed A., Mikhailidis, Dimitri P., Yassin, Hanaa Z., Dobutović, Branislava, Smiljanić, Katarina, Soskić, Sanja S., Mousa, Shaker A., Rizzo, Manfredi, Isenović, Esma R., "Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome" in Current Pharmaceutical Design, 17, no. 33 (2011):3699-3712,
https://doi.org/10.2174/138161211798220882 . .

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 . .