S6K1, arginase-II, and vascular endothelial aging
Description: Aging instead the vasoprotective NO, a situation calledeNOS-uncoupling, is involved in vascular aging. Although studies suggest that enhancedarginase activity (arginase-II in humans and mice) causes eNOS-uncoupling, itis still debatable, whether this is due to depletion of L-arginine for eNOS. Importantly,chronic L-arginine supplementation paradoxically induces endothelial cell agingand increases mortality in patients with myocardial infarction or withperipheral artery disease. In addition, our study also shows that hyperactiveS6K1 emzymatic activity is present in aging endothelial cells and causes eNOS-uncoupling.It is, however, not known, how S6K1 causes eNOS-uncoupling and acceleratesendothelial aging. Based on these results, we would like to investigate theroles and molecular/biochemical mechanisms of S6K1 and Arg-II in promotion of eNOS-uncouplingand endothelial aging in cultured cells and animal models. .-2revious studies showed that the enzyme in vascularendothelial cells called endothelial nitric oxide synthase (eNOS) can produce toxicOis aprominent independent risk factor for cardiovascular disease, the underlyingmechanisms of aging-associated cardiovascular diseases are not fully understood, yet. PThis project will explore noval mechanisms ofage-associated cardiovascular diseases. Particularly, how L-arginine therapy isdetrimental for cardiovascular health will be answered. Expected results shall alsojustify therapeutic rationales of targeting S6K1 and Arg-II foraging-associated vascular disease and beyond, since eNOS-uncoupling, increasedS6K1 and enhanced Arg-II activity are also observed under various pathologicalconditions such as atherosclerosis and obesity.
Amount: CHF 402,000
Funding type: research
Funder scheme: Project funding
Start date: 2012-04-01
End date: 2015-06-30
Investigator: Yang, Zhihong
Institution: University of Fribourg – FR
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 10
Funder award ID: 141070
OpenAlex ID: G4266671196