NAD+, Sirtuins, and Cardiovascular Disease

被引:116
作者
Borradaile, Nica M. [2 ]
Pickering, J. Geoffrey [1 ,2 ,3 ,4 ,5 ]
机构
[1] Univ Western Ontario, London Hlth Sci Ctr, London, ON N6A 5A5, Canada
[2] Univ Western Ontario, Robarts Res Inst, Vasc Biol Grp, London, ON N6A 5A5, Canada
[3] Univ Western Ontario, Dept Med, London, ON N6A 5A5, Canada
[4] Univ Western Ontario, Dept Biochem, London, ON N6A 5A5, Canada
[5] Univ Western Ontario, Dept Med Biophys, London, ON N6A 5A5, Canada
基金
加拿大健康研究院;
关键词
Cardiovascular disease; aging; sirtuin; SIRT1; NAD(+); nicotinamide phosphoribosyltransferase; SMOOTH-MUSCLE-CELLS; DEPENDENT HISTONE DEACETYLASE; STIMULATED INSULIN-SECRETION; SMALL-MOLECULE ACTIVATORS; PANCREATIC BETA-CELLS; OXIDATIVE STRESS; LIFE-SPAN; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; MITOCHONDRIAL-FUNCTION; ENDOTHELIAL-CELLS;
D O I
10.2174/138161209787185742
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cardiovascular disease (CVD) is the most prevalent disease worldwide and there is intense interest in pharmaceutical approaches to reduce the burden of this chronic, aging-related condition. The sirtuin (SIRT) family of NAD(+)-dependent protein deacetylases and ADP-ribosyltransferases have emerged as exciting targets for CVD management that can impact the cardiovascular system both directly and indirectly, the latter by modulating whole body metabolism. SIRT1-4 regulate the activities of a variety of transcription factors, coregulators, and enzymes that improve metabolic control in adipose tissue, liver, skeletal muscle, and pancreas, particularly during obesity and aging. SIRT1 and 7 can control myocardial development and resist stress- and aging-associated myocardial dysfunction through the deacetylation of p53 and forkhead box O1 (FoxO1). By modulating the activity of endothelial nitric oxide synthase ( eNOS), FoxO1, and p53, and the expression of angiotensin II type 1 receptor (AT1R), SIRT1 also promotes vasodilatory and regenerative functions in endothelial and smooth muscle cells of the vascular wall. Given the array of potentially beneficial effects of SIRT activation on cardiovascular health, interest in developing specific SIRT agonists is well-substantiated. Because SIRT activity depends on cellular NAD+ availability, enzymes involved in NAD(+) biosynthesis, including nicotinamide phosphoribosyltransferase (Nampt), may also be valuable pharmaceutical targets for managing CVD. Herein we review the actions of the SIRT proteins on the cardiovascular system and consider the potential of modulating SIRT activity and NAD(+) availability to control CVD.
引用
收藏
页码:110 / 117
页数:8
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