Schinzari F, Tesauro M, Cardillo C
Policlinico A. Gemelli, Rome, Italy, Istituto di Patologia Speciale Medica e Semeiotica Medica, Universita Cattolica del Sacro Cuore, Rome, Italy.
Physiol Res. 2018 Jun 27;67(Suppl 1):S69-S81. doi: 10.33549/physiolres.933821.
The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. Impaired vasodilator reactivity has been recognized as an early hemodynamic abnormality in obese patients, but also increased vasoconstrictor tone importantly contributes to their vascular damage. In particular, upregulation of the endothelin (ET)-1 system, consistently reported in these patients, might accelerate atherosclerosis and its complication, given the pro-inflammatory and mitogenic properties of ET-1. In recent years, a number of gut hormones, in addition to their role as modulators of food intake, energy balance, glucose and lipid metabolism, and insulin secretion and action, have demonstrated favorable vascular actions. They increase the bioavailability of vasodilator mediators like nitric oxide, but they have also been shown to inhibit the ET-1 system. These features make gut hormones promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant advantages. Therefore, there is real hope that better understanding of the properties of gut-derived substances might provide more effective therapies for the obesity-related cardiometabolic syndrome.
肥胖对心血管疾病发生和发展的严重影响引发了人们持续不断的努力，以揭示将过多脂肪与血管功能障碍联系起来的机制。血管舒张反应受损已被认为是肥胖患者早期的血流动力学异常，但血管收缩张力增加也对其血管损伤起着重要作用。特别是，这些患者中一直报告的内皮素（ET）-1系统上调，鉴于ET-1的促炎和促有丝分裂特性，可能会加速动脉粥样硬化及其并发症。近年来，一些肠道激素除了作为食物摄入、能量平衡、葡萄糖和脂质代谢以及胰岛素分泌和作用的调节剂外，还表现出有益的血管作用。它们增加了一氧化氮等血管舒张介质的生物利用度，但也已被证明能抑制ET-1系统。这些特性使肠道激素成为针对肥胖的代谢和心血管并发症的有前景的工具，最近的大规模临床试验支持了这一观点，这些试验表明具有心血管潜力的2型糖尿病新药可能转化为临床上的显著优势。因此，人们确实希望更好地了解肠道衍生物质的特性可能为肥胖相关的心脏代谢综合征提供更有效的治疗方法。
