Kee Zizheng, Kodji Xenia, Brain Susan D
Section of Vascular Biology & Inflammation, BHF Centre for Cardiovascular Research, School of Cardiovascular Medicine and Sciences, King's College London, London, United Kingdom.
Front Physiol. 2018 Sep 19;9:1249. doi: 10.3389/fphys.2018.01249. eCollection 2018.
Calcitonin gene-related peptide (CGRP) is a highly potent vasoactive peptide released from sensory nerves, which is now proposed to have protective effects in several cardiovascular diseases. The major α-form is produced from alternate splicing and processing of the calcitonin gene. The CGRP receptor is a complex composed of calcitonin like receptor (CLR) and a single transmembrane protein, RAMP1. CGRP is a potent vasodilator and proposed to have protective effects in several cardiovascular diseases. CGRP has a proven role in migraine and selective antagonists and antibodies are now reaching the clinic for treatment of migraine. These clinical trials with antagonists and antibodies indicate that CGRP does not play an obvious role in the physiological control of human blood pressure. This review discusses the vasodilator and hypotensive effects of CGRP and the role of CGRP in mediating cardioprotective effects in various cardiovascular models and disorders. In models of hypertension, CGRP protects against the onset and progression of hypertensive states by potentially counteracting against the pro-hypertensive systems such as the renin-angiotensin-aldosterone system (RAAS) and the sympathetic system. With regards to its cardioprotective effects in conditions such as heart failure and ischaemia, CGRP-containing nerves innervate throughout cardiac tissue and the vasculature, where evidence shows this peptide alleviates various aspects of their pathophysiology, including cardiac hypertrophy, reperfusion injury, cardiac inflammation, and apoptosis. Hence, CGRP has been suggested as a cardioprotective, endogenous mediator released under stress to help preserve cardiovascular function. With the recent developments of various CGRP-targeted pharmacotherapies, in the form of CGRP antibodies/antagonists as well as a CGRP analog, this review provides a summary and a discussion of the most recent basic science and clinical findings, initiating a discussion on the future of CGRP as a novel target in various cardiovascular diseases.
降钙素基因相关肽（CGRP）是一种从感觉神经释放的高效血管活性肽，目前认为它在多种心血管疾病中具有保护作用。主要的α形式是由降钙素基因的可变剪接和加工产生的。CGRP受体是一个由降钙素样受体（CLR）和单个跨膜蛋白RAMP1组成的复合体。CGRP是一种强效血管舒张剂，目前认为它在多种心血管疾病中具有保护作用。CGRP在偏头痛中已被证实有作用，现在选择性拮抗剂和抗体正进入临床试验用于治疗偏头痛。这些使用拮抗剂和抗体的临床试验表明，CGRP在人体血压的生理调节中并不起明显作用。本综述讨论了CGRP的血管舒张和降压作用，以及CGRP在各种心血管模型和疾病中介导心脏保护作用的机制。在高血压模型中，CGRP通过潜在地对抗诸如肾素 - 血管紧张素 - 醛固酮系统（RAAS）和交感神经系统等促高血压系统，来预防高血压状态的发生和发展。关于其在心力衰竭和缺血等病症中的心脏保护作用，含CGRP的神经分布于整个心脏组织和血管系统，有证据表明这种肽可减轻其病理生理学的各个方面，包括心肌肥大、再灌注损伤、心脏炎症和细胞凋亡。因此，CGRP被认为是一种在应激状态下释放的心脏保护内源性介质，有助于维持心血管功能。随着各种以CGRP抗体/拮抗剂以及CGRP类似物形式的靶向CGRP药物疗法的最新进展，本综述总结并讨论了最新的基础科学和临床研究结果，引发了关于CGRP作为各种心血管疾病新靶点的未来讨论。
