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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

Extracellular matrix controls insulin signaling in mammary epithelial cells through the RhoA/Rok pathway

Lee, Yi-Ju ; Hsu, Tsai-Ching ; Du, Jyun-Yi ; Valentijn, Anthony J. ; Wu, Tung-Yi ; Cheng, Cheng-Fu ; Yang, Zhihong ; Streuli, Charles H.

In: Journal of Cellular Physiology, 2009, vol. 220, no. 2, p. 476-484

Cellular responses are determined by a number of signaling cues in the local microenvironment, such as growth factors and extracellular matrix (ECM). In cultures of mammary epithelial cells (MECs), functional differentiation requires at least two types of signal, lactogenic hormones (i.e., prolactin, insulin, and hydrocortisone) and the specialized ECM, basement membrane (BM). Our previous work...

Université de Fribourg

Endothelial nitric oxide synthase gene transfer inhibits human smooth muscle cell migration via inhibition of Rho A

Largiadèr, Thomas ; Eto, Masato ; Payeli, Sravan K. ; Greutert, Helen ; Viswambharan, Hema ; Lachat, Mario ; Zünd, Gregor ; Yang, Zhihong ; Tanner, Felix C. ; Lüscher, Thomas F.

In: Journal of Cardiovascular Pharmacology, 2008, vol. 52, no. 4, p. 369-374

Smooth muscle cell (SMC) migration contributes to vascular remodeling. Nitric oxide (NO) produced via endothelial NO synthase (eNOS) inhibits SMC migration. This study analyzes signal transduction mechanisms of SMC migration targeted by NO. SMCs were cultured from human saphenous veins, and cell migration was studied using Boyden chambers. PDGF-BB (0.1 to 10 ng/ml) stimulated SMC migration in a...

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...

Université de Fribourg

Sirolimus increases tissue factor expression but not activity in cultured human vascular smooth muscle cells

Zhu, Shengsi ; Viswambharan, Hema ; Gajanayake, Thusitha ; Ming, Xiu-Fen ; Yang, Zhihong

In: BMC Cardiovascular Disorders, 2007, vol. 5, p. 22

Background Sirolimus-eluting stents (CYPHER stents) demonstrated remarkable efficacy in reducing restenosis rates in patients with coronary artery disease. There is a concern of sub-acute and late stent thrombosis. Tissue factor (TF) is critical in thrombosis. This study investigated the effect of sirolimus on TF expression and activity in cultured human vascular smooth muscle cells...

Université de Fribourg

Mutation of the circadian clock gene Per2 alters vascular endothelial function

Viswambharan, Hema ; Carvas, João Miguel ; Antic, Vladan ; Marecic, Ana ; Jud, Corinne ; Zaugg, Christian E. ; Ming, Xiu-Fen ; Montani, Jean-Pierre ; Albrecht, Urs ; Yang, Zhihong

In: Circulation, 2007, vol. 115, p. 2188-2195

Background— The circadian clock regulates biological processes including cardiovascular function and metabolism. In the present study, we investigated the role of the circadian clock gene Period2 (Per2) in endothelial function in a mouse model. Methods and Results— Compared with the wild-type littermates, mice with Per2 mutation exhibited impaired...

Université de Fribourg

Endothelial arginase: a new target in atherosclerosis

Yang, Zhihong ; Ming, Xiu-Fen

In: Current Hypertension Reports, 2006, vol. 8, no. 1, p. 54-59

Decreased endothelial nitric oxide (NO) bioavailability as it relates to endothelial dysfunction plays an important role in various cardiovascular disorders, including athero­sclerosis. Recent research has provided evidence that endothelial dysfunction in atherosclerosis is not primarily caused by decreased endothelial NO synthase (eNOS) gene expression, but rather deregulation of eNOS...

Université de Fribourg

Different vascular smooth muscle cell apoptosis in the human internal mammary artery and the saphenous vein: implications for bypass graft disease

Frischknecht, Karin ; Greutert, Helen ; Weisshaupt, Christian ; Kaspar, Mathias ; Yang, Zhihong ; Lüscher, Thomas F. ; Carrel, Thierry P. ; Tanner, Felix C.

In: Journal of Vascular Research, 2006, vol. 43, no. 4, p. 338-346

The remarkable patency of internal mammary artery (MA) grafts compared to saphenous vein (SV) grafts has been related to different biological properties of the two blood vessels. We examined whether proliferation and apoptosis of vascular smooth muscle cells (VSMC) from human coronary artery bypass vessels differ according to patency rates. Methods and Results: Proliferation rates to serum...

Université de Fribourg

Dimethyl sulfoxide inhibits tissue factor expression, thrombus formation, and vascular smooth muscle cell activation: a potential treatment strategy for drug-eluting stents

Camici, Giovanni G. ; Steffel, Jan ; Akhmedov, Alexander ; Schafer, Nicola ; Baldinger, Jeannette ; Schulz, Urs ; Shojaati, Kushiar ; Matter, Christian M. ; Yang, Zhihong ; Lüscher, Thomas F. ; Tanner, Felix C.

In: Circulation, 2006, vol. 114, no. 14, p. 1512-1521

Background— Subacute stent thrombosis is a major clinical concern, and the search for new molecules to cover stents remains important. Dimethyl sulfoxide (DMSO) is used for preservation of hematopoietic progenitor cells and is infused into patients undergoing bone marrow transplantation. Despite its intravenous application, the impact of DMSO on vascular cells has not been assessed....

Université de Fribourg

Endothelial nitric oxide synthase gene transfer restores endothelium–dependent relaxations and attenuates lesion formation in carotid arteries in apolipoprotein E–deficient mice

Mujynya-Ludunge, Kathi ; Viswambharan, Hema ; Driscoll, Robert ; Ming, Xiu-Fen ; Segesser, Ludwig K. von ; Kappenberger, Lukas ; Yang, Zhihong ; Vassalli, Giuseppe

In: Basic Research in Cardiology, 2005, vol. 100(2), p. 102

Nitric oxide (NO) and monocyte chemoattractant protein–1 (MCP-1) exert partly opposing effects in vascular biology. NO plays pleiotropic vasoprotective roles including vasodilation and inhibition of platelet aggregation, smooth muscle cell proliferation, and endothelial monocyte adhesion, the last effect being mediated by MCP–1 downregulation. Early stages of arteriosclerosis are associated...