Department of Cardiovascular Disease, Tor Vergata University of Rome, Rome, Italy.
IRCCS Neuromed, Pozzilli, Isernia, Italy.
Oxid Med Cell Longev. 2017;2017:7348372. doi: 10.1155/2017/7348372. Epub 2017 Oct 15.
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein that belongs to the uncoupling protein family and plays an important role in lowering mitochondrial membrane potential and dissipating metabolic energy with prevention of oxidative stress accumulation. In the present article, we will review the evidence that UCP2, as a consequence of its roles within the mitochondria, represents a critical player in the predisposition to vascular disease development in both animal models and in humans, particularly in relation to obesity, diabetes, and hypertension. The deletion of the UCP2 gene contributes to atherosclerosis lesion development in the knockout mice, also showing significantly shorter lifespan. The UCP2 gene downregulation is a key determinant of higher predisposition to renal and cerebrovascular damage in an animal model of spontaneous hypertension and stroke. In contrast, UCP2 overexpression improves both hyperglycemia- and high-salt diet-induced endothelial dysfunction and ameliorates hypertensive target organ damage in SHRSP. Moreover, drugs (fenofibrate and sitagliptin) and several vegetable compounds (extracts from Brassicaceae, berberine, curcumin, and capsaicin) are able to induce UCP2 expression level and to exert beneficial effects on the occurrence of vascular damage. As a consequence, UCP2 becomes an interesting therapeutic target for the treatment of common human vascular diseases.
解偶联蛋白 2（UCP2）是一种线粒体内膜蛋白，属于解偶联蛋白家族，在降低线粒体膜电位和消耗代谢能以防止氧化应激积累方面发挥重要作用。在本文中，我们将回顾证据表明，UCP2 作为其在线粒体中的作用的结果，代表了动物模型和人类中血管疾病发展易感性的关键因素，特别是与肥胖症、糖尿病和高血压有关。UCP2 基因的缺失导致敲除小鼠动脉粥样硬化病变的发展，也显示出明显更短的寿命。UCP2 基因下调是自发性高血压和中风动物模型中肾脏和脑血管损伤更高易感性的关键决定因素。相比之下，UCP2 的过表达可改善自发性高血压大鼠的高血糖和高盐饮食诱导的内皮功能障碍，并改善高血压靶器官损伤。此外，药物（非诺贝特和西他列汀）和几种植物化合物（芸苔属植物提取物、小檗碱、姜黄素和辣椒素）能够诱导 UCP2 的表达水平，并对血管损伤的发生产生有益的影响。因此，UCP2 成为治疗常见人类血管疾病的一个有趣的治疗靶点。
