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Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers
Sowmya Venkatasubramanian1, Radzi Mohd Noh, Shruti Daga
1Centre for Cardiovascular Science, University of Edinburgh, UK. s.venkat@ed.ac.uk
Background:
We examined the effect of the oral SIRT1 activator SRT2104 on cardiovascular function in otherwise healthy cigarette smokers.
Methods And Results:
Twenty-four otherwise healthy cigarette smokers participated in a randomized double-blind, placebo-controlled crossover 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 at the end of each treatment period together with an assessment of forearm blood flow during intra-arterial bradykinin, acetylcholine, and sodium nitroprusside infusions. Three hours postdose, mean plasma SRT2104 concentration was 1328 ± 748 ng/mL after 28 days of active treatment. Compared with 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 cholesterol (-10 ± 17 versus 3 ± 21 mg/dL), and triglyceride (-39.8 ± 77 versus 13.3 ± 57 mg/dL) concentrations (P<0.05 for all). 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). No significant differences in fibrinolytic or blood flow parameters were observed between placebo and SRT2014.
Conclusions:
SRT2104 appears to be safe and well tolerated and associated with an improved lipid profile without demonstrable differences in vascular or platelet function in otherwise healthy cigarette smokers.
Clinical Trial Registration:
http://www.clinicaltrials.gov. Unique identifier: NCT01031108.
Insights
The SIRT1 activator SRT2104 improved lipid profiles in smokers but did not affect vascular or platelet function. This oral treatment demonstrated safety and tolerability in the study population.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Metabolic Health
Background:
- Cigarette smoking negatively impacts cardiovascular health.
- SIRT1 activators are being investigated for therapeutic potential.
- The study focuses on the effects of SRT2104 in smokers.
Purpose of the Study:
- To evaluate the cardiovascular effects of the oral SIRT1 activator SRT2104.
- To assess the safety and tolerability of SRT2104 in cigarette smokers.
- To determine the impact of SRT2104 on lipid profiles and vascular function.
Main Methods:
- A randomized, double-blind, placebo-controlled crossover trial was conducted.
- Twenty-four healthy cigarette smokers received 28 days of SRT2104 or placebo.
- Cardiovascular parameters, lipid profiles, and blood markers were measured.
Main Results:
- SRT2104 treatment led to significant reductions in total cholesterol, LDL cholesterol, and triglycerides.
- No significant differences were observed in fibrinolytic factors or forearm blood flow.
- SRT2104 was found to be safe and well-tolerated by participants.
Conclusions:
- SRT2104 demonstrates potential for improving lipid profiles in cigarette smokers.
- The study suggests SRT2104 is safe and well-tolerated in this population.
- No significant impact on vascular or platelet function was detected with SRT2104 treatment.
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