TY  - JOUR
AU  - Smiljanić, Katarina
AU  - Obradović, Milan
AU  - Jovanovic, Aleksandra
AU  - Popović-Đorđević, Jelena
AU  - Dobutović, Branislava
AU  - Jevremovic, Danimir
AU  - Marche, Pierre
AU  - Isenovic, Esma R.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1853
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.
PB  - Springer, Dordrecht
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 and Jovanovic, Aleksandra and Popović-Đorđević, Jelena and Dobutović, Branislava and Jevremovic, Danimir and Marche, Pierre and Isenovic, 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.",
publisher = "Springer, Dordrecht",
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., Jovanovic, A., Popović-Đorđević, J., Dobutović, B., Jevremovic, D., Marche, P.,& Isenovic, E. R.. (2014). Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2. in Molecular and Cellular Biochemistry
Springer, Dordrecht., 396(1-2), 147-160.
https://doi.org/10.1007/s11010-014-2151-y

Smiljanić K, Obradović M, Jovanovic A, Popović-Đorđević J, Dobutović B, Jevremovic D, Marche P, Isenovic 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, Jovanovic, Aleksandra, Popović-Đorđević, Jelena, Dobutović, Branislava, Jevremovic, Danimir, Marche, Pierre, Isenovic, 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  - Popović, Milan
AU  - Smiljanić, Katarina
AU  - Dobutović, Branislava
AU  - Syrovets, Tatiana
AU  - Simmet, Thomas
AU  - Isenovic, Esma R.
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1220
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.
PB  - Springer, Dordrecht
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 Isenovic, 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.",
publisher = "Springer, Dordrecht",
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.,& Isenovic, E. R.. (2012). Thrombin and vascular inflammation. in Molecular and Cellular Biochemistry
Springer, Dordrecht., 359(1-2), 301-313.
https://doi.org/10.1007/s11010-011-1024-x

Popović M, Smiljanić K, Dobutović B, Syrovets T, Simmet T, Isenovic 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, Isenovic, 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  - Isenovic, Esma R.
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1243
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.
PB  - Springer, Dordrecht
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 Isenovic, 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.",
publisher = "Springer, Dordrecht",
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.,& Isenovic, E. R.. (2012). Human cytomegalovirus infection and atherothrombosis. in Journal of Thrombosis and Thrombolysis
Springer, Dordrecht., 33(2), 160-172.
https://doi.org/10.1007/s11239-011-0662-x

Popović M, Smiljanić K, Dobutović B, Syrovets T, Simmet T, Isenovic 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, Isenovic, 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  - Dobutović, Branislava
AU  - Smiljanić, Katarina
AU  - Soskić, Sanja
AU  - Dungen, Hans-Dirk
AU  - Isenović, Esma
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3918
AB  - Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO) generation. NO is a free radical which reacts with various molecules to cause multiple biological effects. It is clear that the generation and actions of NO under physiological and pathophysiological conditions are exquisitely regulated and extend to almost every cell type and function within the circulation. While the molecule mediates many physiological functions, an excessive presence of NO is toxic to cells. The enzyme NOS, constitutively or inductively, catalyses the production of NO in several biological systems. NO is derived not only from NOS isoforms but also from NOS-independent sources. In mammals, to date, three distinct NOS isoforms have been identified: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). The molecular structure, enzymology and pharmacology of these enzymes have been well defined, and reveal critical roles for the NOS system in a variety of important physiological processes. This review focuses on recent advances in the understanding of the interactions between NOS enzymes and pathophysiology of cardiovascular diseases (CVD) and the role of NO agonists as potential therapeutic agents in treatment of CVD.
PB  - Bentham Open
T2  - The Open Nitric Oxide Journal
T1  - Nitric Oxide and its Role in Cardiovascular Diseases
VL  - 3
IS  - 1
SP  - 65
EP  - 71
DO  - 10.2174/1875042701103010065
ER  - 

@article{
author = "Dobutović, Branislava and Smiljanić, Katarina and Soskić, Sanja and Dungen, Hans-Dirk and Isenović, Esma",
year = "2011",
abstract = "Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO) generation. NO is a free radical which reacts with various molecules to cause multiple biological effects. It is clear that the generation and actions of NO under physiological and pathophysiological conditions are exquisitely regulated and extend to almost every cell type and function within the circulation. While the molecule mediates many physiological functions, an excessive presence of NO is toxic to cells. The enzyme NOS, constitutively or inductively, catalyses the production of NO in several biological systems. NO is derived not only from NOS isoforms but also from NOS-independent sources. In mammals, to date, three distinct NOS isoforms have been identified: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). The molecular structure, enzymology and pharmacology of these enzymes have been well defined, and reveal critical roles for the NOS system in a variety of important physiological processes. This review focuses on recent advances in the understanding of the interactions between NOS enzymes and pathophysiology of cardiovascular diseases (CVD) and the role of NO agonists as potential therapeutic agents in treatment of CVD.",
publisher = "Bentham Open",
journal = "The Open Nitric Oxide Journal",
title = "Nitric Oxide and its Role in Cardiovascular Diseases",
volume = "3",
number = "1",
pages = "65-71",
doi = "10.2174/1875042701103010065"
}

Dobutović, B., Smiljanić, K., Soskić, S., Dungen, H.,& Isenović, E.. (2011). Nitric Oxide and its Role in Cardiovascular Diseases. in The Open Nitric Oxide Journal
Bentham Open., 3(1), 65-71.
https://doi.org/10.2174/1875042701103010065

Dobutović B, Smiljanić K, Soskić S, Dungen H, Isenović E. Nitric Oxide and its Role in Cardiovascular Diseases. in The Open Nitric Oxide Journal. 2011;3(1):65-71.
doi:10.2174/1875042701103010065 .

Dobutović, Branislava, Smiljanić, Katarina, Soskić, Sanja, Dungen, Hans-Dirk, Isenović, Esma, "Nitric Oxide and its Role in Cardiovascular Diseases" in The Open Nitric Oxide Journal, 3, no. 1 (2011):65-71,
https://doi.org/10.2174/1875042701103010065 . .

TY  - JOUR
AU  - Haidara, Mohamed
AU  - Mikhailidis, Dimitri P.
AU  - Yassin, Hanaa Z.
AU  - Dobutović, Branislava
AU  - Smiljanić, Katarina
AU  - Soskic, Sanja
AU  - Mousa, Shaker A.
AU  - Rizzo, Manfredi
AU  - Isenovic, Esma R.
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1242
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.
PB  - Bentham Science Publ Ltd, Sharjah
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 and Mikhailidis, Dimitri P. and Yassin, Hanaa Z. and Dobutović, Branislava and Smiljanić, Katarina and Soskic, Sanja and Mousa, Shaker A. and Rizzo, Manfredi and Isenovic, 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.",
publisher = "Bentham Science Publ Ltd, Sharjah",
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., Mikhailidis, D. P., Yassin, H. Z., Dobutović, B., Smiljanić, K., Soskic, S., Mousa, S. A., Rizzo, M.,& Isenovic, E. R.. (2011). Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome. in Current Pharmaceutical Design
Bentham Science Publ Ltd, Sharjah., 17(33), 3699-3712.
https://doi.org/10.2174/138161211798220882

Haidara M, Mikhailidis DP, Yassin HZ, Dobutović B, Smiljanić K, Soskic S, Mousa SA, Rizzo M, Isenovic 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, Mikhailidis, Dimitri P., Yassin, Hanaa Z., Dobutović, Branislava, Smiljanić, Katarina, Soskic, Sanja, Mousa, Shaker A., Rizzo, Manfredi, Isenovic, 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  - Isenovic, Esma R.
AU  - Fretaud, Maxence
AU  - Dobutović, Branislava
AU  - Sudar, Emina
AU  - Smiljanić, Katarina
AU  - Zarić, Božidarka L.
AU  - Trpkovic, Andreja
AU  - Marche, Pierre
PY  - 2009
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/612
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.
PB  - Academic Press Ltd- Elsevier Science Ltd, London
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 = "Isenovic, Esma R. and Fretaud, Maxence and Dobutović, Branislava and Sudar, Emina and Smiljanić, Katarina and Zarić, Božidarka L. and Trpkovic, 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.",
publisher = "Academic Press Ltd- Elsevier Science Ltd, London",
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"
}

Isenovic, E. R., Fretaud, M., Dobutović, B., Sudar, E., Smiljanić, K., Zarić, B. L., Trpkovic, 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
Academic Press Ltd- Elsevier Science Ltd, London., 33(3), 386-392.
https://doi.org/10.1016/j.cellbi.2009.01.010

Isenovic ER, Fretaud M, Dobutović B, Sudar E, Smiljanić K, Zarić BL, Trpkovic 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 .

Isenovic, Esma R., Fretaud, Maxence, Dobutović, Branislava, Sudar, Emina, Smiljanić, Katarina, Zarić, Božidarka L., Trpkovic, 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 . .