Intermedin protects against myocardial ischemia-reperfusion injury in hyperlipidemia rats

Abstract

ABSTRACT. Hyperlipidemia is a well-established risk factor for the development of coronary atherosclerosis, while intermedin (IMD) has been identified as a novel calcitonin/calcitonin gene-related peptide family member involved in cardiovascular protection. However, whether IMD protects against hyperlipidemia-associated myocardial ischemia/reperfusion (MI/R) injury is unknown. We established a hyperlipidemia model using Sprague-Dawley rats, and created a MI/R condition by ligating the cardiac left circumflex artery. The possible pathophysiological role of IMD and its physiological function in MI/R was further studied. The level of IMD significantly decreased in hyperlipidemia rats (P < 0.05). After MI/R, the IMD level was increased both in the plasma and myocardial tissue of hyperlipidemia rats compared to the sham-operated rats (P < 0.001). As evaluated by the activity of LDH, CK-MB, MDA and SOD, additional IMD was revealed to alleviate MI/R heart injury in hyperlipidemia rats (P < 0.05). By regulating the process of cardiomyocyte apoptosis and inflammatory reaction, IMD could perform an important role in cardio-protection, especially against hyperlipidemia-associated MI/R injury. Additional IMD could protect cardiac myocytes against MI/R injury via reduction of apoptosis and inflammation in the hyperlipidemia rat model, and thus, it may play a potential role as a novel therapeutic target for cardiac ischemic injury in hyperlipidemic patients.

Intermedin_1–53 Protects Against Myocardial Fibrosis by Inhibiting Endoplasmic Reticulum Stress and Inflammation Induced by Homocysteine in Apolipoprotein E-Deficient Mice

“…Moreover, IMD 1–53 treatment reversed Hcy-activated TGF- β 1 expression in the ApoE-/- mouse myocardium and in CFs. These anti-inflammatory effects of IMD were identical to the other researches for diabetes, hyperlipidemia, and hypertension 32, 34, 35) . It was reported that NF- κ B and JNK signal pathway played significant roles in proinflammatory process.…”

“…In addition, IMD 1–53 can protect against myocardial ischemia injury and vascular smooth muscle cell calcification by attenuating ERS 30, 31) . IMD can inhibit inflammation in diabetic and hyperlipidemia rats and rats with salt-sensitive hypertension 32–34) . However, whether IMD prevents myocardial fibrosis by inhibiting ERS and inflammation induced by Hcy in ApoE-/- mice has not been investigated.…”

Adrenomedullin 2/intermedin: a putative drug candidate for treatment of cardiometabolic diseases

“…ADM2/IMD 1–53 protects cardiomyocytes against I/R‐induced injury by inhibiting ER stress, oxidative stress and apoptosis in a PI3K/Akt‐ and ERK‐dependent pathway (Song et al , ; Teng et al , ; Zhao et al , ). In isolated hearts, ADM2/IMD 1–40 , ADM2/IMD 1–47 and ADM2/IMD 1–53 ameliorated the I/R‐induced myocardial injury and decreased cardiac function (Yang et al , ). Further studies have shown that ADM2/IMD 1–47 protects cardiomyocytes and cardiac microvascular endothelium from I/R‐induced injury via AM 1 receptors (Bell et al , ; Bell et al , ).…”

Cardioprotective effect of Salvianolic acid B on acute myocardial infarction by promoting autophagy and neovascularization and inhibiting apoptosis

“…Whole protein extracts were obtained by homogenizing ventricle samples that were flash-frozen in liquid nitrogen in whole cell lysis buffer (50 mM Tris-HCl, pH 7.5, 50 mM 2-mercaptoethanol, 5 mM EGTA, 2 mM EDTA, 1% NP-40, 0.1% sodium dodecyl sulfate polyacrylamide (SDS), 0.5% deoxycholic acid, 10 mM NaF, 1 mM PMSF, 25 mg/ml leupeptin, 2 mg/ml aprotinin). [36] Protein concentrations were determined by Bio-Rad (Richmond, CA, USA) protein assay according to the manufacturer's instructions. Fifty micrograms of total protein from each sample was separated by SDS-PAGE and transferred onto polyvinylidene fluoride membranes using a semidry transfer system from Fisher (Suwanee, GA, USA).…”