Jin Zhe, Tan Qindong, Sun Bei
State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing, China.
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Cell Biochem Funct. 2018 Jan;36(1):18-26. doi: 10.1002/cbf.3313.
Coronary slow flow phenomenon (CSFP) is a coronary microvascular disorder with an increasing morbidity, and currently, available therapies are of limited clinical value for its cure. Hence, it is urgent to find a novel approach to CSFP treatment. Several studies show that endothelial dysfunction plays a critical role in the aetiology of CSFP. Telmisartan (TMST) is a clinically available anti-hypertensive medicine and has shown its potential properties for improving vascular endothelial function. Thus, we aimed to investigate the effect of TMST on endothelial dysfunction in CSFP, Endothelial-dependent flow-mediated vasodilation, serum levels of nitric oxide, adiponectin, and endothelin-1 were surveyed before and after 3 months of TMST treatment. And the percentages of vasodilator response to acetylcholine (Ach) were detected after 12 weeks of TMST treatment. Compare with pretreatment, flow-mediated vasodilation, nitric oxide, and adiponectin were substantially improved after TMST treatment; meanwhile, endothelin-1 was decreased in the TMST group (all P < .01). Compared with the model group, the vasodilator response to Ach was enormously increased after TMST intervention. Additionally, administration of SU11274 or GW9662 would partially reverse the protective effects of TMST on accumulative concentration-vasodilator responses to Ach (P < .01). We demonstrated that administration of TMST could remarkably increase the mRNA and/or protein levels of hepatocyte growth factor, mesenchymal-epithelial transition factor, peroxisome proliferation-activated receptor γ, whereas dramatically diminish mRNA and/or protein levels of p-JNK1/2, mitogen-activated protein kinase, and nuclear factor kappa B (P < .05). Our results thus implicate that TMST ameliorates endothelial dysfunction in CSFP. It is suggested that TSMF may play an important role in the medication of CSFP.
冠状动脉慢血流现象（CSFP）是一种发病率不断上升的冠状动脉微血管疾病，目前现有的治疗方法对其治愈的临床价值有限。因此，迫切需要找到一种治疗CSFP的新方法。多项研究表明，内皮功能障碍在CSFP的病因中起关键作用。替米沙坦（TMST）是一种临床可用的抗高血压药物，已显示出其改善血管内皮功能的潜在特性。因此，我们旨在研究TMST对CSFP内皮功能障碍的影响，在TMST治疗3个月前后测量内皮依赖性血流介导的血管舒张、血清一氧化氮、脂联素和内皮素-1水平。在TMST治疗12周后检测对乙酰胆碱（Ach）的血管舒张反应百分比。与治疗前相比，TMST治疗后血流介导的血管舒张、一氧化氮和脂联素显著改善；同时，TMST组内皮素-1降低（所有P < 0.01）。与模型组相比，TMST干预后对Ach的血管舒张反应大幅增加。此外，给予SU11274或GW9662会部分逆转TMST对Ach累积浓度-血管舒张反应的保护作用（P < 0.01）。我们证明，给予TMST可显著增加肝细胞生长因子、间充质-上皮转化因子、过氧化物酶体增殖物激活受体γ的mRNA和/或蛋白质水平，而显著降低p-JNK1/2、丝裂原活化蛋白激酶和核因子κB的mRNA和/或蛋白质水平（P < 0.05）。因此，我们的结果表明TMST可改善CSFP中的内皮功能障碍。提示TSMF可能在CSFP的药物治疗中起重要作用。
