Centre for Cardiovascular Science, University of Edinburgh, UK.
J Am Heart Assoc. 2013 Jun 14;2(3):e000042. doi: 10.1161/JAHA.113.000042.
We examined the effect of the oral SIRT1 activator SRT2104 on cardiovascular function in otherwise healthy cigarette smokers.
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.
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.
http://www.clinicaltrials.gov. Unique identifier: NCT01031108.
我们研究了口服 SIRT1 激活剂 SRT2104 对健康吸烟人群心血管功能的影响。
24 名健康吸烟人群参与了一项随机、双盲、安慰剂对照交叉试验，接受 28 天的口服 SRT2104（2.0 g/天）或匹配的安慰剂治疗。在基线和每个治疗期结束时，测量血浆 SRT2104 浓度、血清脂质谱、血浆纤溶因子以及血小板和单核细胞激活标志物，并评估在动脉内给予缓激肽、乙酰胆碱和硝普钠时的前臂血流。给药后 3 小时，在 28 天的活性治疗后，平均血浆 SRT2104 浓度为 1328±748ng/ml。与安慰剂相比，SRT2104 给药期间血清脂质谱改善，总胆固醇（-11.6±20 与 6±21mg/dL）、低密度脂蛋白胆固醇（-10±17 与 3±21mg/dL）和甘油三酯（-39.8±77 与 13.3±57mg/dL）浓度降低（所有 P<0.05）。所有血管扩张剂均引起血流剂量依赖性增加（P<0.0001），且在每个治疗期之间相似（所有 P>0.05）。在安慰剂和 SRT2014 之间，纤溶或血流参数无显著差异。
SRT2104 似乎安全且耐受良好，与健康吸烟人群的脂质谱改善相关，而血管或血小板功能无明显差异。
