Sirtuin1 inhibitor attenuates hypertension in spontaneously hypertensive rats: role of Giα proteins and nitroxidative stress.

Background: We recently showed that vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) exhibit overexpression of Sirtuin1 (Sirt1) that contributes to the enhanced expression of Giα proteins implicated in the development of hypertension in SHR.

Method: The present study investigated if the inhibition of Sirt1 could also ameliorate hypertension in SHR and explore the underlying molecular mechanisms. For this study, a selective inhibitor of Sirt1, EX-527 (5 mg/kg of body weight), was injected intraperitoneally into 8-week-old SHR and age-matched Wistar Kyoto (WKY) rats twice per week for 3 weeks.

Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce.

Obesity is considered an important factor for many chronic diseases, including diabetes, cardiovascular disease and cancer. The expansion of adipose tissue in obesity is due to an increase in both adipocyte progenitor differentiation and mature adipocyte cell size. Adipocytes, however, are thought to be unable to divide or enter the cell cycle.

Sirtuin1 contributes to the overexpression of Giα proteins and hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats.

Background: We earlier demonstrated that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit the overexpression of Giα proteins and hyperproliferation that is attributed to the enhanced levels of endogenous angiotensin II (Ang II). In addition, the implication of Sirtuin1 (Sirt1) a histone deacetylase class III family in Ang II-induced hypertension has also been shown. We recently demonstrated that Ang II increased the expression of Sirt1 in aortic VSMC that contributed to the overexpression of Giα proteins.