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  - http://intor.torlakinstitut.com/handle/123456789/786
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
EP  - 3712
IS  - 33
SP  - 3699
VL  - 17
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",
pages = "3712-3699",
number = "33",
volume = "17",
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  - http://intor.torlakinstitut.com/handle/123456789/754
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
EP  - 392
IS  - 3
SP  - 386
VL  - 33
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",
pages = "392-386",
number = "3",
volume = "33",
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 . .