Abstract 11363: Cardiovascular Effects of a Novel SIRT 1 Activator, SRT2104, in Otherwise Healthy Cigarette Smokers
Background: The sirtuins have several beneficial effects on inflammation, metabolism and aging that may improve cardiovascular health. We examined the effect of the oral SIRT1 activator, SRT2104, on cardiovascular function in cigarette smokers.
Methods: Twenty-four otherwise healthy male and female cigarette smokers participated in a randomised, double-blind, placebo-controlled, cross-over trial and received 28 days of oral SRT2104 (2.0 g/day) or matched placebo. Plasma SRT2104 concentrations, serum lipid profile, plasma fibrinolytic factors and markers of platelet and monocyte activation were measured at baseline and the end of each treatment period together with an assessment of forearm blood flow during intra-arterial bradykinin, acetylcholine and sodium nitroprusside infusions.
Results: Mean plasma SRT2104 concentration at 3 hours post dose were 1328±748 ng/mL after 28 days of active treatment. In comparison to placebo, serum lipid profile improved during SRT2104 administration with reductions in serum total cholesterol (-11.6±20 versus +6±21 mg/dL), low-density lipoprotein (-10±17 versus +3±21 mg/dL) cholesterol concentrations and triglyceride (-39.8±77 versus +13.3±57 mg/dL) concentrations (P<0.05 for all). No significant differences in fibrinolytic or blood flow parameters were observed between placebo vs. SRT2014. All vasodilators produced a dose-dependent increase in blood flow (P<0.0001) that was similar during each treatment period (P>0.05 for all). In addition, at both visits the non-infused arm showed no change from the initial blood flow measurement at any measurement taken during that visit (P>0.05) and the initial blood flow measurement for the infused arm under saline was not statistically different between the two visits (P>0.05).
Conclusion: For the first time, we have examined the cardiovascular effects of an oral SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers. It appears to be safe and well tolerated, and associated with an improved lipid profile without demonstrable differences on endothelial functional or platelet activation.
- © 2012 by American Heart Association, Inc.