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Université de Fribourg

Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression

Reiner, Martin F. ; Akhmedov, Alexander ; Stivala, Simona ; Keller, Stephan ; Gaul, Daniel S. ; Bonetti, Nicole R. ; Savarese, Gianluigi ; Glanzmann, Martina ; Zhu, Cuicui ; Ruf, Wolfram ; Yang, Zhihong ; Matter, Christian M. ; Lüscher, Thomas F. ; Camici, Giovanni G. ; Beer, Juerg H.

In: Cardiovascular Research, 2017, vol. 113, no. 1, p. 61–69

The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been...

Université de Fribourg

Genetic targeting of arginase-ii in mouse prevents renal oxidative stress and inflammation in diet-induced obesity

Huang, Ji ; Rajapakse, Angana ; Xiong, Yuyan ; Montani, Jean-Pierre ; Verrey, François ; Ming, Xiu-Fen ; Yang, Zhihong

In: Frontiers in Physiology, 2016, vol. 7, p. -

Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L- arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase- II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and...

Université de Fribourg

"En Face" detection of nitric oxide and superoxide in endothelial layer of intact arteries

Yu, Yi ; Xiong, Yuyan ; Montani, Jean-Pierre ; Yang, Zhihong ; Ming, Xiu-Fen

In: Journal of Visualized Experiments, 2016, no. 108, p. -

Endothelium-derived nitric oxide (NO) produced from endothelial NO-synthase (eNOS) is one of the most important vasoprotective molecules in cardiovascular physiology. Dysfunctional eNOS such as uncoupling of eNOS leads to decrease in NO bioavailability and increase in superoxide anion (O₂.−) production, and in turn promotes cardiovascular diseases. Therefore, appropriate...

Université de Fribourg

Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation

Liu, Chang ; Rajapakse, Angana G. ; Riedo, Erwin ; Fellay, Benoit ; Bernhard, Marie-Claire ; Montani, Jean-Pierre ; Yang, Zhihong ; Ming, Xiu-Fen

In: Scientific Reports, 2016, vol. 6, p. 20405

Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in...

Université de Fribourg

P38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-Uncoupling in Obesity

Yu, Yi ; Rajapakse, Angana G. ; Montani, Jean-Pierre ; Yang, Zhihong ; Ming, Xiu-Fen

In: Cardiovascular Diabetology, 2014, vol. 13, no. 1, p. 113

Background Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk...

Université de Fribourg

Arginase‐II induces vascular smooth muscle cell senescence and apoptosis through p66Shc and p53 independently of its l‐arginine ureahydrolase activity: implications for atherosclerotic plaque vulnerability

Xiong, Yuyan ; Yu, Yi ; Montani, Jean‐Pierre ; Yang, Zhihong ; Ming, Xiu‐Fen

In: Journal of the American Heart Association, 2013, vol. 2, no. 4, p. e000096

Background Vascular smooth muscle cell (VSMC) senescence and apoptosis are involved in atherosclerotic plaque vulnerability. Arginase‐II (Arg‐II) has been shown to promote vascular dysfunction and plaque vulnerability phenotypes in mice through uncoupling of endothelial nitric oxide synthase and activation of macrophage inflammation. The function of Arg‐II in VSMCs with respect to plaque...

Université de Fribourg

Caffeine induces endothelial tissue factor expression via phosphatidylinositol 3-kinase inhibition

Gebhard, C. ; Holy, E. W. ; Camici, Giovanni G. ; Akhmedov, Alexander ; Stämpfli, S. F. ; Stähli, B. E. ; Rickenbach, B. von ; Breitenstein, A. ; Greutert, Helen ; Yang, Zhihong ; Lüscher, Thomas F. ; Tanner, Felix C.

In: Thrombosis and Haemostasis, 2012, vol. 107, no. 5, p. 803-1007

Tissue factor (TF) is the key activator of coagulation and is involved in acute coronary syndromes. Caffeine is often reported to increase cardiovascular risk; however, its effect on cardiovascular morbidity and mortality is controversial. Hence, this study was designed to investigate the impact of caffeine on endothelial TF expression in vitro . Caffeine concentration-dependently enhanced TF...

Université de Fribourg

Positive crosstalk between arginase-II and S6K1 in vascular endothelial inflammation and aging

Yepuri, Gautham ; Velagapudi, Srividya ; Xiong, Yuyan ; Rajapakse, Angana G. ; Montani, Jean-Pierre ; Ming, Xiu-Fen ; Yang, Zhihong

In: Aging Cell, 2012, p. -

Augmented activities of both arginase and S6K1 are involved in endothelial dysfunction in aging. This study was to investigate whether or not there is a crosstalk between arginase and S6K1 in endothelial inflammation and aging in senescent human umbilical vein endothelial cells and in aging mouse models. We show increased arginase-II (Arg-II) expression/activity in senescent endothelial cells....

Université de Fribourg

Hyperactive S6K1 mediates oxidative stress and endothelial dysfunction in aging: inhibition by resveratrol

Rajapakse, Angana Gupta ; Yepuri, Gautham ; Carvas, João M. ; Stein, Sokrates ; Matter, Christian M. ; Scerri, Isabelle ; Ruffieux, Jean ; Montani, Jean-Pierre ; Ming, Xiu-Fen ; Yang, Zhihong

In: PLoS ONE, 2011, vol. 6, no. 4, p. e19237

Mammalian target of rapamycin (mTOR)/S6K1 signalling emerges as a critical regulator of aging. Yet, a role of mTOR/S6K1 in aging-associated vascular endothelial dysfunction remains unknown. In this study, we investigated the role of S6K1 in aging-associated endothelial dysfunction and effects of the polyphenol resveratrol on S6K1 in aging endothelial cells. We show here that senescent endothelial...

Université de Fribourg

Opposing and uncoupling effects of mTOR and S6K1 in the regulation of endothelial tissue factor expression

Ming, Xiu-Fen ; Rajapakse, Angana Gupta ; Carvas, João Miguel ; Ruffieux, Jean ; Yang, Zhihong

In: Febs Letters, 2010, vol. 58, no. 1, p. 135-140

Rapamycin has been reported to enhance tissue factor (TF) expression. The present study investigated roles of mammalian target of rapamycin (mTOR) and its downstream S6K1 in this process. We showed here that, consistent with rapamycin, knocking-down mTOR enhanced thrombin-induced TF mRNA and protein levels, whereas silencing S6K1 mitigated up-regulation of TF protein but not TF mRNA level. The...