Ewart Marie-Ann, Kennedy Simon
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, G12 8QQ, UK.
Cardiovasc Hematol Agents Med Chem. 2012 Sep;10(3):190-211. doi: 10.2174/187152512802651015.
Cardiovascular complications are the leading cause of death and morbidity in patients with diabetes; accounting for around 7 out of 10 of all causes of death in this population. Returning patients to normoglycaemia alone has been shown to have little effect on cardiovascular end points, therefore new therapies and strategies are required in order to reduce the incidence and improve outcomes of cardiovascular disease in diabetic individuals. The metabolic enzyme AMP-activated protein kinase (AMPK) has emerged in recent years as an attractive potential therapeutic target for diabetic vascular disease, and studies have shown improved endothelial and smooth muscle cell function following AMPK activation. Additionally, improved lipid profiles, reduced hypertrophic cardiomyocyte growth and protection from cardiac ischaemia-reperfusion injury have also been observed as beneficial outcomes of AMPK therapy. In this review we will discuss in detail the potential downstream targets of AMPK activation in the cardiovascular system. We will also provide an overview of long-known and newly discovered direct and indirect AMPK activators, as well as novel synthesised AMPK-activating compounds, which will highlight the potential for further exploiting AMPK in a therapeutic context for cardiovascular disease in diabetes.
心血管并发症是糖尿病患者死亡和发病的主要原因；在该人群的所有死因中，约占十分之七。仅使患者恢复正常血糖水平已被证明对心血管终点影响甚微，因此需要新的治疗方法和策略来降低糖尿病个体心血管疾病的发病率并改善其预后。代谢酶AMP激活蛋白激酶（AMPK）近年来已成为糖尿病血管疾病一个颇具吸引力的潜在治疗靶点，研究表明，激活AMPK后内皮细胞和平滑肌细胞功能得到改善。此外，脂质谱改善、肥厚性心肌细胞生长减少以及免受心脏缺血再灌注损伤，也被视为AMPK治疗的有益结果。在这篇综述中，我们将详细讨论AMPK激活在心血管系统中的潜在下游靶点。我们还将概述长期已知和新发现的直接和间接AMPK激活剂，以及新合成的AMPK激活化合物，这将突出在治疗糖尿病心血管疾病方面进一步利用AMPK的潜力。
