TY  - JOUR
AU  - Savić, Kristina
AU  - Zafirović, Sonja
AU  - Resanović, Ivana
AU  - Sudar, Emina
AU  - Maravić-Stojković, Vera
AU  - Putniković, Biljana
AU  - Isenović, Esma R.
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10320
AB  - Biomarkeri predstavljaju indikatore normalnih bioloških procesa, patogenih procesa ili farmakoloških odgovora na terapijske intervencije. Interleukin-6 (IL6, engl. Interleukin-6) je biomarker, čija sinteza može biti aktivirana različitim stimulusima, kao što su: interferon-g (IFN-g, engl. Interferon-g), faktor tumorske nekroze (TNF, engl. Tumor Necrosis Factor) i/ili interleukin-1 (IL-1, engl. Interleukin-1). IL-6 svoje efekte ostvaruje preko IL-6 receptora (IL-6R, engl. IL-6 Receptor). Pokazano je da kod transgenih miševa, kod kojih je indukovana ekspresija IL-6 i IL-6R, dolazi do hipertrofije miokarda. U mehanizmu hipertrofije miokarda bitnu ulogu ima i novootkriveni kardiotrofin1 (CT-1, engl. Cardiotrophin-1) koji je jedan od članova IL-6 familije. Aktivnost IL-6 vezuje se za razvoj aneurizme abdominalne aorte (AAA, engl. Abdominal Aortic Aneurysm), zapravo, pokazano je da su aneurizme mesta odakle cirkuliše IL-6, a takođe se smatra da je koncentracija IL-6 u pozitivnoj korelaciji sa dijametrim AAA. C-reaktivni protein (CRP, engl. CReactive Protein) je jedan od mnogobrojnih biomarkera kardiovaskularnih bolesti. Uloga CRP-a je u nastanku i progresiji kardiovaskularnih bolesti. Lokalna produkcija CRP-a od strane glatkih mišićnih i endotelnih ćelija krvnog suda, u velikoj meri utiče na razvoj procesa ateroskleroze. Važnu ulogu u nastanku ateroskleroze, osim CRP-a, ima i oksidovani lipoprotein male gustine (ox-LDL, engl. Oxidized Low Density Lipoprotein). Oksidaciju LDL-a vrše različiti enzimi. Ox-LDL nakon što prođe u intimu krvnog suda indukuje sakupljanje monocita, tj. monociti se prevode u makrofage koji vezuju ox-LDL. Kada se makrofagi napune ox-LDL-om, dolazi do pokretanja signala ćelijske smrti i stvaraju se forme penušavih ćelija koje čine početni deo aterosklerotičnog plaka. Nova saznanja o mehamizmu delovanja kao i uloge biomerkera u nastanku kardiovaskularnih bolesti, svakako će pružiti jednu od mogućnosti prevencije nastanka ovih poremećaja, a takođe i adekvatnu terapiju u lecenju kardiovaskularnih oboljenja, što i jeste jedan od glavnih ciljeva intezivnih istraživanja u oblasti biomarkera. U ovom preglednom članku, opisana su tri biomarkera kardiovaskularnih bolesti: IL-6, CRP i LDL.
AB  - Biomarkers are indicators of normal biological processes, pathogenic processes or pharmacologic responses to therapeutic interventions. Interleukin-6 (IL - 6) is a biomarker whose synthesis could be activated by various stimuli, such as interferon-g (IFN - g), tumor necrosis factor (TNF) and/or interleukin - 1 (IL - 1). IL - 6 achieves its effects through the IL-6 receptor (IL - 6R). It has been shown that transgenic mice, which have induced expression of IL - 6 and IL - 6R develop myocardial hypertrophy. In myocardial hypertrophy, an important role is played by a newly discovered cardiotrophin-1, a member of the IL - 6 family. The activity of IL - 6 is associated with the development of abdominal aortic aneurysm (AAA); in fact, it has been shown that the concentration of IL - 6 positively correlates with AAA diameters. C-reactive protein (CRP) is one of the biomarkers of cardiovascular diseases. Local production of CRP by the smooth muscular and endothelial cells of the vessel leads to the development of atherosclerosis to a large extent. Oxidized low-density lipoprotein (ox - LDL) also has an important role in the development of atherosclerosis. After penetrating the intima of the vessel, ox - LDL induces monocyte collection, i.e. monocytes are translated into macrophages that bind ox - LDL. Having filled the macrophages with ox - LDL, the signals of cell death are activated, which leads to the creation of foamy cells that make up the initial part of the atherosclerotic plaque. New knowledge about the mechanism of action and the role of biomarkers in the development of cardiovascular diseases will certainly provide an opportunity to prevent the onset of these disorders, as well as an adequate therapy in the treatment of cardiovascular diseases, which is one of the main goals of intensive research in the field of biomarkers.
T2  - Medicinska istraživanja
T1  - Biomarkeri u kardiovaskularnim bolestima
T1  - Biomarkers of cardiovascular diseases
VL  - 47
IS  - 2
SP  - 11
EP  - 19
DO  - 10.5937/MedIst1302011S
ER  - 

@article{
author = "Savić, Kristina and Zafirović, Sonja and Resanović, Ivana and Sudar, Emina and Maravić-Stojković, Vera and Putniković, Biljana and Isenović, Esma R.",
year = "2013",
abstract = "Biomarkeri predstavljaju indikatore normalnih bioloških procesa, patogenih procesa ili farmakoloških odgovora na terapijske intervencije. Interleukin-6 (IL6, engl. Interleukin-6) je biomarker, čija sinteza može biti aktivirana različitim stimulusima, kao što su: interferon-g (IFN-g, engl. Interferon-g), faktor tumorske nekroze (TNF, engl. Tumor Necrosis Factor) i/ili interleukin-1 (IL-1, engl. Interleukin-1). IL-6 svoje efekte ostvaruje preko IL-6 receptora (IL-6R, engl. IL-6 Receptor). Pokazano je da kod transgenih miševa, kod kojih je indukovana ekspresija IL-6 i IL-6R, dolazi do hipertrofije miokarda. U mehanizmu hipertrofije miokarda bitnu ulogu ima i novootkriveni kardiotrofin1 (CT-1, engl. Cardiotrophin-1) koji je jedan od članova IL-6 familije. Aktivnost IL-6 vezuje se za razvoj aneurizme abdominalne aorte (AAA, engl. Abdominal Aortic Aneurysm), zapravo, pokazano je da su aneurizme mesta odakle cirkuliše IL-6, a takođe se smatra da je koncentracija IL-6 u pozitivnoj korelaciji sa dijametrim AAA. C-reaktivni protein (CRP, engl. CReactive Protein) je jedan od mnogobrojnih biomarkera kardiovaskularnih bolesti. Uloga CRP-a je u nastanku i progresiji kardiovaskularnih bolesti. Lokalna produkcija CRP-a od strane glatkih mišićnih i endotelnih ćelija krvnog suda, u velikoj meri utiče na razvoj procesa ateroskleroze. Važnu ulogu u nastanku ateroskleroze, osim CRP-a, ima i oksidovani lipoprotein male gustine (ox-LDL, engl. Oxidized Low Density Lipoprotein). Oksidaciju LDL-a vrše različiti enzimi. Ox-LDL nakon što prođe u intimu krvnog suda indukuje sakupljanje monocita, tj. monociti se prevode u makrofage koji vezuju ox-LDL. Kada se makrofagi napune ox-LDL-om, dolazi do pokretanja signala ćelijske smrti i stvaraju se forme penušavih ćelija koje čine početni deo aterosklerotičnog plaka. Nova saznanja o mehamizmu delovanja kao i uloge biomerkera u nastanku kardiovaskularnih bolesti, svakako će pružiti jednu od mogućnosti prevencije nastanka ovih poremećaja, a takođe i adekvatnu terapiju u lecenju kardiovaskularnih oboljenja, što i jeste jedan od glavnih ciljeva intezivnih istraživanja u oblasti biomarkera. U ovom preglednom članku, opisana su tri biomarkera kardiovaskularnih bolesti: IL-6, CRP i LDL., Biomarkers are indicators of normal biological processes, pathogenic processes or pharmacologic responses to therapeutic interventions. Interleukin-6 (IL - 6) is a biomarker whose synthesis could be activated by various stimuli, such as interferon-g (IFN - g), tumor necrosis factor (TNF) and/or interleukin - 1 (IL - 1). IL - 6 achieves its effects through the IL-6 receptor (IL - 6R). It has been shown that transgenic mice, which have induced expression of IL - 6 and IL - 6R develop myocardial hypertrophy. In myocardial hypertrophy, an important role is played by a newly discovered cardiotrophin-1, a member of the IL - 6 family. The activity of IL - 6 is associated with the development of abdominal aortic aneurysm (AAA); in fact, it has been shown that the concentration of IL - 6 positively correlates with AAA diameters. C-reactive protein (CRP) is one of the biomarkers of cardiovascular diseases. Local production of CRP by the smooth muscular and endothelial cells of the vessel leads to the development of atherosclerosis to a large extent. Oxidized low-density lipoprotein (ox - LDL) also has an important role in the development of atherosclerosis. After penetrating the intima of the vessel, ox - LDL induces monocyte collection, i.e. monocytes are translated into macrophages that bind ox - LDL. Having filled the macrophages with ox - LDL, the signals of cell death are activated, which leads to the creation of foamy cells that make up the initial part of the atherosclerotic plaque. New knowledge about the mechanism of action and the role of biomarkers in the development of cardiovascular diseases will certainly provide an opportunity to prevent the onset of these disorders, as well as an adequate therapy in the treatment of cardiovascular diseases, which is one of the main goals of intensive research in the field of biomarkers.",
journal = "Medicinska istraživanja",
title = "Biomarkeri u kardiovaskularnim bolestima, Biomarkers of cardiovascular diseases",
volume = "47",
number = "2",
pages = "11-19",
doi = "10.5937/MedIst1302011S"
}

Savić, K., Zafirović, S., Resanović, I., Sudar, E., Maravić-Stojković, V., Putniković, B.,& Isenović, E. R.. (2013). Biomarkeri u kardiovaskularnim bolestima. in Medicinska istraživanja, 47(2), 11-19.
https://doi.org/10.5937/MedIst1302011S

Savić K, Zafirović S, Resanović I, Sudar E, Maravić-Stojković V, Putniković B, Isenović ER. Biomarkeri u kardiovaskularnim bolestima. in Medicinska istraživanja. 2013;47(2):11-19.
doi:10.5937/MedIst1302011S .

Savić, Kristina, Zafirović, Sonja, Resanović, Ivana, Sudar, Emina, Maravić-Stojković, Vera, Putniković, Biljana, Isenović, Esma R., "Biomarkeri u kardiovaskularnim bolestima" in Medicinska istraživanja, 47, no. 2 (2013):11-19,
https://doi.org/10.5937/MedIst1302011S . .

TY  - JOUR
AU  - Bojić, Tijana
AU  - Radak, Đorđe J.
AU  - Putniković, Biljana
AU  - Alavantić, Dragan
AU  - Isenović, Esma R.
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5279
T2  - Vojnosanitetski pregled
T1  - Methodology of monitoring cardiovascular regulation
VL  - 69
IS  - 12
SP  - 1084
EP  - 1090
DO  - 10.2298/VSP110707019B
ER  - 

@article{
author = "Bojić, Tijana and Radak, Đorđe J. and Putniković, Biljana and Alavantić, Dragan and Isenović, Esma R.",
year = "2012",
journal = "Vojnosanitetski pregled",
title = "Methodology of monitoring cardiovascular regulation",
volume = "69",
number = "12",
pages = "1084-1090",
doi = "10.2298/VSP110707019B"
}

Bojić, T., Radak, Đ. J., Putniković, B., Alavantić, D.,& Isenović, E. R.. (2012). Methodology of monitoring cardiovascular regulation. in Vojnosanitetski pregled, 69(12), 1084-1090.
https://doi.org/10.2298/VSP110707019B

Bojić T, Radak ĐJ, Putniković B, Alavantić D, Isenović ER. Methodology of monitoring cardiovascular regulation. in Vojnosanitetski pregled. 2012;69(12):1084-1090.
doi:10.2298/VSP110707019B .

Bojić, Tijana, Radak, Đorđe J., Putniković, Biljana, Alavantić, Dragan, Isenović, Esma R., "Methodology of monitoring cardiovascular regulation" in Vojnosanitetski pregled, 69, no. 12 (2012):1084-1090,
https://doi.org/10.2298/VSP110707019B . .

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  - Sudar, Emina
AU  - Dobutović, Branislava
AU  - Milosavljević, Tijana
AU  - Putniković, Biljana
AU  - Gluvić, Zoran
AU  - Isenović, Esma R.
PY  - 2009
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3804
AB  - Insulin (INS) and beta-estradiol (E(2)) have vascular effects partially through stimulation of protein kinase B (Akt) phosphorylation. Employing adult rat cardiomyocytes (ARC), the effects of acute (15 min) stimulation with INS (10 mIU/ml) and prolonged (2 hours and 24 hours) stimulation with E(2) alone or in combination, were assessed with respect to protein levels of Akt. Exposure to INS for 15 minutes enhanced Akt Ser(473) phosphorylation. The combined treatment had a greater effect on Akt phosphorylation then the effect of INS alone. The results suggest that INS and E(2) may interact through Akt in regulating metabolic processes.
T2  - Acta Chimica Slovenica
T1  - Interactive Effects of Insulin and beta-Estradiol on Protein Kinase B Phosphorylation in Adult Rat Cardiomyocytes
VL  - 56
IS  - 3
SP  - 723
EP  - 728
UR  - https://hdl.handle.net/21.15107/rcub_vinar_3804
ER  - 

@article{
author = "Sudar, Emina and Dobutović, Branislava and Milosavljević, Tijana and Putniković, Biljana and Gluvić, Zoran and Isenović, Esma R.",
year = "2009",
abstract = "Insulin (INS) and beta-estradiol (E(2)) have vascular effects partially through stimulation of protein kinase B (Akt) phosphorylation. Employing adult rat cardiomyocytes (ARC), the effects of acute (15 min) stimulation with INS (10 mIU/ml) and prolonged (2 hours and 24 hours) stimulation with E(2) alone or in combination, were assessed with respect to protein levels of Akt. Exposure to INS for 15 minutes enhanced Akt Ser(473) phosphorylation. The combined treatment had a greater effect on Akt phosphorylation then the effect of INS alone. The results suggest that INS and E(2) may interact through Akt in regulating metabolic processes.",
journal = "Acta Chimica Slovenica",
title = "Interactive Effects of Insulin and beta-Estradiol on Protein Kinase B Phosphorylation in Adult Rat Cardiomyocytes",
volume = "56",
number = "3",
pages = "723-728",
url = "https://hdl.handle.net/21.15107/rcub_vinar_3804"
}

Sudar, E., Dobutović, B., Milosavljević, T., Putniković, B., Gluvić, Z.,& Isenović, E. R.. (2009). Interactive Effects of Insulin and beta-Estradiol on Protein Kinase B Phosphorylation in Adult Rat Cardiomyocytes. in Acta Chimica Slovenica, 56(3), 723-728.
https://hdl.handle.net/21.15107/rcub_vinar_3804

Sudar E, Dobutović B, Milosavljević T, Putniković B, Gluvić Z, Isenović ER. Interactive Effects of Insulin and beta-Estradiol on Protein Kinase B Phosphorylation in Adult Rat Cardiomyocytes. in Acta Chimica Slovenica. 2009;56(3):723-728.
https://hdl.handle.net/21.15107/rcub_vinar_3804 .

Sudar, Emina, Dobutović, Branislava, Milosavljević, Tijana, Putniković, Biljana, Gluvić, Zoran, Isenović, Esma R., "Interactive Effects of Insulin and beta-Estradiol on Protein Kinase B Phosphorylation in Adult Rat Cardiomyocytes" in Acta Chimica Slovenica, 56, no. 3 (2009):723-728,
https://hdl.handle.net/21.15107/rcub_vinar_3804 .

TY  - JOUR
AU  - Sudar, Emina
AU  - Velebit, Mena
AU  - Gluvić, Zoran
AU  - Žakula, Zorica
AU  - Lazić, Emilija
AU  - Vuksanovic-Topic, Ljiljana
AU  - Putniković, Biljana
AU  - Neskovic, Aleksandar
AU  - Isenović, Esma R.
PY  - 2008
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3442
AB  - Causal relationship between sodium and hypertension has been proposed and various changes in Na+, K+-ATPase (sodium pump) activity have been described in established primary hypertension. A number of direct vascular effects of estradiol have been reported, including its impact on the regulation of sodium pump activity and vasomotor tone. The effects of estradiol involve the activation of multiple signaling cascades, including phosphatydil inositol-3 kinase (PI3K) and p42/44 mitogen-activated protein kinase (p42/44 MAPK). In addition, some of the effects of estradiol have been linked to activity of cytosolic phospholipase A(2) (cPLA(2)). One possible cardioprotective mechanism of estradiol involves of the interaction between estradiol and the rennin-angiotensin system (RAS). Elevated circulating and tissue levels of angiotensin II (Ang II) have been implicated in the development of hypertension and heart failure. The aim of our investigation was to elucidate the signaling mechanisms employed by estradiol and Ang II in mediating sodium pump, in vascular smooth muscle cells (VSMC). The aim of our investigation was to elucidate the signaling mechanisms employed by estradiol and Ang II in mediating sodium pump activity/expression in VSMC, with particular emphasis on PI3K/cPLA(2)/p42/44(MAPK) signaling pathways. Our primary hypothesis is that estradiol stimulates sodium. pump activity/expression in VSMC via PI3K/cPLA(2)/p42/44(MAPK) dependent mechanism and, that impaired estradiol-stimulated sodium pump activity/expression in hypertensive rodent models (i.e. SHR), Ang II-mediated vascular impairment of estradiol is related to a decrease ability of estradiol to stimulate the PI3K/cPLA(2)/p42/44(MAPK) signaling pathways. An important corollary to this hypothesis is that in hypertensive state (i.e. SHR rats) the decreasing in ACE enzyme activity and/or AT1 receptor expression caused by administration of estradiol is accompanying with abrogated ability of Ang 11 to decrease IRS-1/PI3K association, and consequent PI3K/cPLA(2)/p42/44(MAPK) activity and associated sodium pump activity/expression. A clear characterization of how Ang II attenuates estradiol signaling may lead to a better understanding of the molecular mechanism(s) underlying pathophysiological conditions such as hypertension and to understanding how certain pathophysiological situations affect sodium pump activity/expression in VSMC. (c) 2008 Elsevier Ltd. All rights reserved.
T2  - Journal of Theoretical Biology
T1  - Hypothetical mechanism of sodium pump regulation by estradiol under primary hypertension
VL  - 251
IS  - 4
SP  - 584
EP  - 592
DO  - 10.1016/j.jtbi.2007.12.023
ER  - 

@article{
author = "Sudar, Emina and Velebit, Mena and Gluvić, Zoran and Žakula, Zorica and Lazić, Emilija and Vuksanovic-Topic, Ljiljana and Putniković, Biljana and Neskovic, Aleksandar and Isenović, Esma R.",
year = "2008",
abstract = "Causal relationship between sodium and hypertension has been proposed and various changes in Na+, K+-ATPase (sodium pump) activity have been described in established primary hypertension. A number of direct vascular effects of estradiol have been reported, including its impact on the regulation of sodium pump activity and vasomotor tone. The effects of estradiol involve the activation of multiple signaling cascades, including phosphatydil inositol-3 kinase (PI3K) and p42/44 mitogen-activated protein kinase (p42/44 MAPK). In addition, some of the effects of estradiol have been linked to activity of cytosolic phospholipase A(2) (cPLA(2)). One possible cardioprotective mechanism of estradiol involves of the interaction between estradiol and the rennin-angiotensin system (RAS). Elevated circulating and tissue levels of angiotensin II (Ang II) have been implicated in the development of hypertension and heart failure. The aim of our investigation was to elucidate the signaling mechanisms employed by estradiol and Ang II in mediating sodium pump, in vascular smooth muscle cells (VSMC). The aim of our investigation was to elucidate the signaling mechanisms employed by estradiol and Ang II in mediating sodium pump activity/expression in VSMC, with particular emphasis on PI3K/cPLA(2)/p42/44(MAPK) signaling pathways. Our primary hypothesis is that estradiol stimulates sodium. pump activity/expression in VSMC via PI3K/cPLA(2)/p42/44(MAPK) dependent mechanism and, that impaired estradiol-stimulated sodium pump activity/expression in hypertensive rodent models (i.e. SHR), Ang II-mediated vascular impairment of estradiol is related to a decrease ability of estradiol to stimulate the PI3K/cPLA(2)/p42/44(MAPK) signaling pathways. An important corollary to this hypothesis is that in hypertensive state (i.e. SHR rats) the decreasing in ACE enzyme activity and/or AT1 receptor expression caused by administration of estradiol is accompanying with abrogated ability of Ang 11 to decrease IRS-1/PI3K association, and consequent PI3K/cPLA(2)/p42/44(MAPK) activity and associated sodium pump activity/expression. A clear characterization of how Ang II attenuates estradiol signaling may lead to a better understanding of the molecular mechanism(s) underlying pathophysiological conditions such as hypertension and to understanding how certain pathophysiological situations affect sodium pump activity/expression in VSMC. (c) 2008 Elsevier Ltd. All rights reserved.",
journal = "Journal of Theoretical Biology",
title = "Hypothetical mechanism of sodium pump regulation by estradiol under primary hypertension",
volume = "251",
number = "4",
pages = "584-592",
doi = "10.1016/j.jtbi.2007.12.023"
}

Sudar, E., Velebit, M., Gluvić, Z., Žakula, Z., Lazić, E., Vuksanovic-Topic, L., Putniković, B., Neskovic, A.,& Isenović, E. R.. (2008). Hypothetical mechanism of sodium pump regulation by estradiol under primary hypertension. in Journal of Theoretical Biology, 251(4), 584-592.
https://doi.org/10.1016/j.jtbi.2007.12.023

Sudar E, Velebit M, Gluvić Z, Žakula Z, Lazić E, Vuksanovic-Topic L, Putniković B, Neskovic A, Isenović ER. Hypothetical mechanism of sodium pump regulation by estradiol under primary hypertension. in Journal of Theoretical Biology. 2008;251(4):584-592.
doi:10.1016/j.jtbi.2007.12.023 .

Sudar, Emina, Velebit, Mena, Gluvić, Zoran, Žakula, Zorica, Lazić, Emilija, Vuksanovic-Topic, Ljiljana, Putniković, Biljana, Neskovic, Aleksandar, Isenović, Esma R., "Hypothetical mechanism of sodium pump regulation by estradiol under primary hypertension" in Journal of Theoretical Biology, 251, no. 4 (2008):584-592,
https://doi.org/10.1016/j.jtbi.2007.12.023 . .

TY  - JOUR
AU  - Žakula, Zorica
AU  - Korićanac, Goran
AU  - Putniković, Biljana
AU  - Markovic, Ljiljana
AU  - Isenović, Esma R.
PY  - 2007
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/3205
AB  - Insulin-like growth factor-1 (IGF-1) is a hormone and growth factor closely related to insulin. The autocrine/paracrine actions of IGF-1 involve activation of inducible nitric oxide synthase (iNOS) and the Na(+), K(+)-ATPase sodium pump in cardiovascular tissues. Data from literature indicate that iNOS is expressed in vascular smooth muscle cells (VSMC) and that IGF- 1 -induced release of NO is both rapid and delayed. We hypothesize that impaired IGF-1 -induced sodium pump activity/ expression in rats with type 1 diabetes is related to activation of phosphatidytinositol 3 kinase (PI3K)/cytosolic phospholipase 2 (cPLA(2))/protein kinase B (Akt) signaling, and that IGF-1 prevents acute and chronic dysfunction of iNOS and sodium pump activity in a chemically induced model of type 1 diabetes, the streptozotocin -treated rat heart (STZ). Understanding how iNOS and sodium pump activity are regulated by IGF-1 activation of the PI3K/cPLA(2)/Akt cascade should provide novel and fundamental knowledge regarding the regulatory actions of IGF-1 in promoting vasodilation. Since insulin resistance is currently a major focus of research, the use of IGF-1 to improve insulin resistance and glucose metabolism has opened a new arena for treatment of comorbid conditions. Future investigations should now focus on mechanisms of action of IGF-1 and its clinical applicability. (c) 2007 Elsevier Ltd. All rights reserved.
T2  - Medical Hypotheses
T1  - Regulation of the inducible nitric oxide synthase and sodium pump in type 1 diabetes
VL  - 69
IS  - 2
SP  - 302
EP  - 306
DO  - 10.1016/j.mehy.2006.11.045
ER  - 

@article{
author = "Žakula, Zorica and Korićanac, Goran and Putniković, Biljana and Markovic, Ljiljana and Isenović, Esma R.",
year = "2007",
abstract = "Insulin-like growth factor-1 (IGF-1) is a hormone and growth factor closely related to insulin. The autocrine/paracrine actions of IGF-1 involve activation of inducible nitric oxide synthase (iNOS) and the Na(+), K(+)-ATPase sodium pump in cardiovascular tissues. Data from literature indicate that iNOS is expressed in vascular smooth muscle cells (VSMC) and that IGF- 1 -induced release of NO is both rapid and delayed. We hypothesize that impaired IGF-1 -induced sodium pump activity/ expression in rats with type 1 diabetes is related to activation of phosphatidytinositol 3 kinase (PI3K)/cytosolic phospholipase 2 (cPLA(2))/protein kinase B (Akt) signaling, and that IGF-1 prevents acute and chronic dysfunction of iNOS and sodium pump activity in a chemically induced model of type 1 diabetes, the streptozotocin -treated rat heart (STZ). Understanding how iNOS and sodium pump activity are regulated by IGF-1 activation of the PI3K/cPLA(2)/Akt cascade should provide novel and fundamental knowledge regarding the regulatory actions of IGF-1 in promoting vasodilation. Since insulin resistance is currently a major focus of research, the use of IGF-1 to improve insulin resistance and glucose metabolism has opened a new arena for treatment of comorbid conditions. Future investigations should now focus on mechanisms of action of IGF-1 and its clinical applicability. (c) 2007 Elsevier Ltd. All rights reserved.",
journal = "Medical Hypotheses",
title = "Regulation of the inducible nitric oxide synthase and sodium pump in type 1 diabetes",
volume = "69",
number = "2",
pages = "302-306",
doi = "10.1016/j.mehy.2006.11.045"
}

Žakula, Z., Korićanac, G., Putniković, B., Markovic, L.,& Isenović, E. R.. (2007). Regulation of the inducible nitric oxide synthase and sodium pump in type 1 diabetes. in Medical Hypotheses, 69(2), 302-306.
https://doi.org/10.1016/j.mehy.2006.11.045

Žakula Z, Korićanac G, Putniković B, Markovic L, Isenović ER. Regulation of the inducible nitric oxide synthase and sodium pump in type 1 diabetes. in Medical Hypotheses. 2007;69(2):302-306.
doi:10.1016/j.mehy.2006.11.045 .

Žakula, Zorica, Korićanac, Goran, Putniković, Biljana, Markovic, Ljiljana, Isenović, Esma R., "Regulation of the inducible nitric oxide synthase and sodium pump in type 1 diabetes" in Medical Hypotheses, 69, no. 2 (2007):302-306,
https://doi.org/10.1016/j.mehy.2006.11.045 . .