van den Heuvel Mieke, Batenburg Wendy W, Danser A H Jan
Division of Pharmacology, Vascular and Metabolic Diseases, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Mol Cell Endocrinol. 2009 Apr 29;302(2):213-8. doi: 10.1016/j.mce.2008.09.010. Epub 2008 Sep 17.
Morbidity and mortality of diabetes mellitus are strongly associated with cardiovascular disease including nephropathy. A discordant tissue renin-angiotensin system (RAS) might be a mediator of the endothelial dysfunction leading to both micro- and macrovascular complications of diabetes. The elevated plasma levels of prorenin in diabetic subjects with microvascular complications might be part of this discordant RAS, especially since the plasma renin levels in diabetes are low. Prorenin, previously thought of as an inactive precursor of renin, is now known to bind to a (pro)renin receptor, thus activating locally angiotensin-dependent and -independent pathways. In particular, the stimulation of the transforming growth factor-beta (TGF-beta) system by prorenin could be an important contributor to diabetic disease complications. This review discusses the concept of the prorenin-(pro)renin receptor-TGF-beta(1) axis, concluding that interference with this pathway might be a next logical step in the search for new therapeutic regimens to reduce diabetes-related morbidity and mortality.
糖尿病的发病率和死亡率与包括肾病在内的心血管疾病密切相关。失调的组织肾素-血管紧张素系统（RAS）可能是导致糖尿病微血管和大血管并发症的内皮功能障碍的介质。患有微血管并发症的糖尿病患者血浆中血管紧张素原水平升高可能是这种失调的RAS的一部分，特别是因为糖尿病患者的血浆肾素水平较低。血管紧张素原以前被认为是肾素的无活性前体，现在已知它能与（前）肾素受体结合，从而激活局部的血管紧张素依赖性和非依赖性途径。特别是，血管紧张素原对转化生长因子-β（TGF-β）系统的刺激可能是糖尿病疾病并发症的一个重要促成因素。本综述讨论了血管紧张素原-（前）肾素受体-TGF-β（1）轴的概念，得出结论认为，干扰这一途径可能是寻找降低糖尿病相关发病率和死亡率的新治疗方案的下一个合理步骤。
