Healthy Blood Vessel Blog

Fasting improves endothelial function

Through the same mechanisms that point to extended lifespan through periodic 24-48hr fasts - or even chronic under eating.. or better yet, a chronic caloric deficit caused by intense amounts of exercise.. however here its just fasting thats studied.

1: Cell Cycle. 2008 Jul 15;7(14):2117-22. Epub 2008 May 8. Links

Emerging roles of SIRT1 in vascular endothelial homeostasis.

Potente M, Dimmeler S.

Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Frankfurt, Germany.

Sir2 is a NAD(+)-dependent deacetylase, which regulates life span in multiple model organisms in response to caloric restriction. Mammalian homologues of Sir2 comprise a family of seven proteins termed sirtuins (SIRT1-SIRT7), which have gained considerable attention for their impact on several important physiological processes associated with metabolism and stress resistance. In addition, recent studies point to SIRT1 as a key regulator of vascular endothelial homeostasis controlling angiogenesis, vascular tone and endothelial dysfunction. Here, we review the emerging role of SIRT1 as an important modulator of signaling networks critical for maintaining vascular endothelial homeostasis and discuss SIRT1 as a potential therapeutic target for cardiovascular diseases in the adult.

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Second study..

SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase.

Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

Reduced caloric intake decreases arterial blood pressure in healthy individuals and improves endothelium-dependent vasodilation in obese and overweight individuals. The SIRT1 protein deacetylase mediates many of the effects of calorie restriction (CR) on organismal lifespan and metabolic pathways. However, the role of SIRT1 in regulating endothelium-dependent vasomotor tone is not known. Here we show that SIRT1 promotes endothelium-dependent vasodilation by targeting endothelial nitric oxide synthase (eNOS) for deacetylation. SIRT1 and eNOS colocalize and coprecipitate in endothelial cells, and SIRT1 deacetylates eNOS, stimulating eNOS activity and increasing endothelial nitric oxide (NO). SIRT1-induced increase in endothelial NO is mediated through lysines 496 and 506 in the calmodulin-binding domain of eNOS. Inhibition of SIRT1 in the endothelium of arteries inhibits endothelium-dependent vasodilation and decreases bioavailable NO. Finally, CR of mice leads to deacetylation of eNOS. Our results demonstrate that SIRT1 plays a fundamental role in regulating endothelial NO and endothelium-dependent vascular tone by deacetylating eNOS. Furthermore, our results provide a possible molecular mechanism connecting the effects of CR on the endothelium and vascular tone to SIRT1-mediated deacetylation of eNOS.

posted by jeff.check @ 1:04 AM