Abstract
The treatment of hypertension and heart failure remains a major challenge to healthcare providers. Despite therapeutic advances, heart failure affects more than 26 million people worldwide and is increasing in prevalence due to an ageing population. Similarly, despite an improvement in blood pressure management, largely due to pharmacological interventions, hypertension remains a silent killer. This is in part due to its ability to contribute to heart failure. Development of novel therapies will likely be at the forefront of future cardiovascular studies to address these unmet needs. Calcitonin gene-related peptide (CGRP) is a 37 amino acid potent vasodilator with positive-ionotropic and -chronotropic effects. It has been reported to have beneficial effects in hypertensive and heart failure patients. Interestingly, changes in plasma CGRP concentration in patients after myocardial infarction, heart failure, and in some forms of hypertension, also support a role for CGRP on hemodynamic functions. Rodent studies have played an important role thus far in delineating mechanisms involved in CGRP-induced cardioprotection. However, due to the short plasma half-life of CGRP, these well documented beneficial effects have often proven to be acute and transient. Recent development of longer lasting CGRP agonists may therefore offer a practical solution to investigating CGRP further in cardiovascular disease in vivo. Furthermore, pre-clinical murine studies have hinted at the prospect of cardioprotective mechanisms of CGRP which is independent of its hypotensive effect. Here, we discuss past and present evidence of vascular-dependent and -independent processes by which CGRP could protect the vasculature and myocardium against cardiovascular dysfunction.
Highlights
The discovery of Calcitonin gene-related peptide (CGRP) mRNA in the rat hypothalamus by Amara et al (1982) sparked a series of studies exploring the effect of CGRP in the central and peripheral systems, where it is widely distributed
These findings suggest that α-CGRP may be able to offer protection to compensate for pathophysiological processes such as endothelial dysfunction, which contributes to hypertension and cardiovascular disease
A wide spectrum of in vitro, ex vivo, in vivo and human studies have highlighted the therapeutic potential of CGRP in various pathophysiological conditions within the cardiovascular system
Summary
The discovery of Calcitonin gene-related peptide (CGRP) mRNA in the rat hypothalamus by Amara et al (1982) sparked a series of studies exploring the effect of CGRP in the central and peripheral systems, where it is widely distributed. It was found that CGRP has two structurally similar isoforms – the α and β, which are encoded by two distinct genes (Amara et al, 1985). Both isoforms are primarily located in sensory C- and Aδ-fibers (Gibson et al, 1984), and it is generally accepted that despite 94% sequence identity between the two isoforms, β-CGRP synthesis and expression is concentrated around the enteric nervous system, immune cells and pituitary gland (Steenbergh et al, 1985; Brain and Grant, 2004) whereas α-CGRP is primarily involved in the central and peripheral nervous systems, and is the more extensively studied isoform in cardiovascular studies. This review aims to discuss past and present literature on CGRP in hypertension and heart failure to stimulate thought on the future of CGRP and cardiovascular research, with a particular focus on α-CGRP
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