Downregulation of Endogenous Intermedin Augmented Myocardial Injury in Rats with Ischemia/Reperfusion

Abstract

tonin/calcitonin gene-related peptide (CGRP) family [ 5 , 6 ]. The human IMD gene encodes a prepropeptide of 148 amino acids with a signal peptide for secretion at the N terminus. IMD 1-53 can be generated from prepro-IMD by proteolytic cleavage at Arg93-Arg94 [ 7 , 8 ]. Two other bioactive polypeptides, IMD 1-47 and IMD 8-47 , are generated from prepro-IMD. The biological action of IMD is mediated by calcitonin receptor-like receptor (CRLR, the 7 transmembrane G proteincoupled receptor) and receptor activity-modifying proteins (RAMPs). IMD is a potent systemic and pulmonary vasodilator, infl uences regional blood fl ow and augments cardiac contractility [ 9 ]. IMD was found to dose-dependently augment cardiac perfusion and function and increase blood fl ow of the mesenterium, kidney, and hind limb [ 10 , 11 ]. IMD 1-53 inhibited cardiac fi broblast activation induced by angiotensin II [ 12 ] and improved viability of human aortic endothelial cells by inhibiting apoptosis and increasing the density of capillaries and arterioles in the ischemic hind limb of rats [ 13 , 14 ]. IMD stabilized pulmonary microvascular permeability that was increased during infl ammation and hypoxia. Furthermore, IMD decreased the generation of oxy-* These authors contributed equally to this manuscript.

Intermedin protects against myocardial ischemia-reperfusion injury in hyperlipidemia rats

“…Significantly, our study demonstrated that MI/R increased caspase-3 and Bax protein expression in hyperlipidemia animals, while the activity of Bcl-2 was decreased in the meantime, suggesting that hyperlipidemia rats showed exacerbated apoptosis after MI/R compared to non-hyperlipidemia rats. Moreover, previous studies have demonstrated that IMD administration decreases MI/R-induced cardiomyocyte apoptosis Du et al, 2011), and that myocardial injury may be exacerbated by downregulated IMD during early reperfusion (Teng et al, 2013). Our research further reinforced these reports, which demonstrated that the alteration of apoptosis-associated genes after MI/R was attenuated by additional IMD treatment, indicating that IMD has an anti-apoptotic effect on the MI/R heart injury in hyperlipidemia models.…”

Intermedin protects against myocardial ischemia-reperfusion injury in diabetic rats

“…Previous studies demonstrate IMD administration decreases MI/R-induced cardiomyocyte apoptosis [11,17], and myocardial injury may be exacerbated by downregulated IMD during early reperfusion [62]. We demonstrate MI/R increased caspase-3 activity and Bax protein expression in diabetic animals compared to control, which was attenuated by IMD administration.…”

Intermedin1–53 attenuates vascular calcification in rats with chronic kidney disease by upregulation of α-Klotho

“…53 Finally, within a wide range of concentration, IMD has various cardiovascular protective effects, including decreasing blood pressure, 53 inhibiting calcification, 22 enhancing cardiac contractile function, 54 and protecting against schemia/reperfusion injury. 21 In summary, we provide evidence that the paracrine/ endocrine factor IMD 1-53 attenuates vascular calcification by upregulating a-Klotho level via the CRLR/RAMP3 receptor complex and activating cAMP/PKA signaling and partly by improving kidney function. The vasoactive peptide IMD 1-53 , an endogenous calcification inhibitor, may open new avenues for preventing vascular calcification in CKD.…”

“…20 The expression profile of IMD and its receptors is disturbed in different cardiovascular diseases. 21,22 IMD is considered a potential endogenous protective peptide of the cardiovascular system by activating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. 23 Several studies showed that IMD 1-53 protects against myocardial ischemia-reperfusion, strengthens the contractility of the left ventricle, and inhibits angiotensin II-induced hypertrophy in cultured neonatal rat ventricular myocytes.…”