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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: the emerging therapeutic target for vascular oxidative stress and inflammation

Yang, Zhihong ; Ming, Xiu-Fen

In: Frontiers in Inflammation, 2013, vol. 4, p. 149

Oxidative stress and inflammation in the vascular wall are essential mechanisms of atherosclerosis and vascular dysfunctions associated with risk factors such as metabolic diseases, aging, hypertension, etc. Evidence has been provided that activation of the vascular endothelial cells in the presence of the risk factors promotes oxidative stress and vascular inflammatory responses, leading to...

Université de Fribourg

mTOR signalling: the molecular interface connecting metabolic stress, aging and cardiovascular diseases

Yang, Zhihong ; Ming, Xiu-Fen

In: Obesity Reviews, 2012, vol. 13, no. S2, p. 58–68

The continuing increase in the prevalence of obesity and metabolic disorders such as type-II diabetes and an accelerating aging population globally will remain the major contributors to cardiovascular mortality and morbidity in the 21st century. It is well known that aging is highly associated with metabolic and cardiovascular diseases. Growing evidence also shows that obesity and metabolic...

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

Perspectives of targeting mTORC1–S6K1 in cardiovascular aging

Ming, Xiu-Fen ; Montani, Jean-Pierre ; Yang, Zhihong

In: Frontiers in Vascular Physiology, 2012, vol. 3, p. 5

The global population aging is accelerating and age-associated diseases including cardiovascular diseases become more challenging. The underlying mechanisms of aging and age-associated cardiovascular dysfunction remain elusive. There are substantial evidences demonstrating a pivotal role of the mammalian target of rapamycin complex 1 (mTORC1) and its down-stream effector S6K1 signaling in...

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...

Université de Fribourg

O-linked β-N-acetylglucosamine during hyperglycemia exerts both anti-inflammatory and pro-oxidative properties in the endothelial system

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

In: Oxidative Medicine & Cellular Longevity, 2009, vol. 2, no. 3, p. 172 - 175

Elevated cellular levels of protein O-linked β-N-acetylglucosamine (O-GlcNAc) through hexosamine biosynthesis pathway (HBP) are suggested to contribute to cardiovascular adverse effects under chronic hyperglycemic condition associated with oxidative stress and inflammation. Conversely, enhancing O-GlcNAc levels have also been demonstrated being protective against myocardial ischemia/reperfusion...

Université de Fribourg

Inhibition of S6K1 accounts partially for the anti-inflammatory effects of the arginase inhibitor L-norvaline

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

In: BMC Cardiovascular Disorders, 2009, vol. 9, no. 12, p. -

Background: Pharmacological inhibition of endothelial arginase-II has been shown to improve endothelial nitric oxide synthase (eNOS) function and reduce atherogenesis in animal models. We investigated whether the endothelial arginase II is involved in inflammatory responses in endothelial cells. Methods: Human endothelial cells were isolated from umbilical veins and stimulated with TNFα (10...

Université de Fribourg

The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects

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

In: American Journal of Physiology - Heart and Circulatory Physiology, 2009, vol. 296, p. H815-H822

Hexosamine biosynthetic pathway (HBP) accounts for some cardiovascular adverse effects of hyperglycemia. We investigated whether the HBP inhibitor azaserine protects against hyperglycemia-induced endothelial damage dependently of HBP. Human endothelial cells isolated from umbilical veins were exposed either to a high (30.5 mmol/l) or low concentration of glucose (5.5 mmol/l) for 4 days, followed...