Epidermal growth factor protects the heart against low-flow ischemia-induced injury

Abstract

The role of ErbB4 and ErbB2 in the heart of adult mammals is well established. The heart also expresses ErbB1 (the epidermal growth factor (EGF) receptor), but this receptor has received less attention. We studied the effect of EGF on the response of isolated mouse heart to low-flow ischemia and reperfusion. Reducing perfusate flow to 10% for 30 min resulted in an increase in anaerobic metabolism and the leakage of lactate dehydrogenase during reperfusion. In addition, left ventricle +dP/dt and developed pressure were depressed (20-25%) during reperfusion. The addition of EGF 5 min before and throughout the ischemic period prevented the increase in anaerobic metabolism and the leakage of intracellular lactate dehydrogenase during reperfusion. EGF improved both +dP/dt and developed pressure during ischemia and prevented the decrease in dP/dt during reperfusion. To determine whether the effect of EGF on cell integrity depends on its effect on contractility, we studied nonbeating isolated myocytes. In these cells, anoxia and reoxygenation reduced cell viability by nearly 25%. EGF prevented such a decrease. Our results indicate that, like ErbB4 and ErbB2, ErbB1 also has an important role in the heart of adult animals.

Gene Expression Analyses during Spontaneous Reversal of Cardiomyopathy in Mice with Repressed Nuclear CUG-BP, Elav-Like Family (CELF) Activity in Heart Muscle

“…KLK1b26 is involved in the maturation of epidermal growth factor (EGF) and renin [ 40 ]. EGF has been shown to be protective against ischemic injury in the heart [ 41 , 42 ]. Renin, on the other hand, is a protease involved in the production of angiotensin II, which induces systemic vasoconstriction, cardiomyocyte hypertrophy, and cardiac fibrosis, changes associated with worsening of ventricular function [ 43 ].…”

Coupling of myocardial stress resistance and signalling to voluntary activity and inactivity

“…, Lorita et al . ), and evidence of involvement in ischaemic preconditioning and adenosinergic protection (Williams‐Pritchard et al . ), suggest that this regulation will impact stress resistance.…”

“…Specifically, we test whether: (i) myocardial stress resistance is consistently coupled to short‐term (3–14 days) elevations and reductions in low‐intensity activity; and (ii) this cardiac coupling can be explained by reversible control of kinase (AKT, ERK1/2, AMPK, GSK3ß), heat shock (HSP27) and membrane receptor (EGFR) proteins common to preconditioning via ischaemia/calorie restriction and associated opioid and cytokine stimuli (Murphy & Steenbergen , Lorita et al . , Williams‐Pritchard et al . , Cai et al .…”

Low-flow ischaemia and reperfusion in rat hearts: energetic of stunning and cardioprotection of genistein

“…[7] The fall in aerobic metabolism seem to be compensated by the anaerobic, as reported in isolated mouse hearts in which reducing the perfusate flow to 10% increased the anaerobic metabolism and leakage of lactate dehydrogenase as well as depressed contractility with 20-25% during reperfusion. [8] In the same species, reducing perfusion flow to 5% of initial induced a mild sublethal injury without cell death, which was independent on the genetical reduction of hexokinase levels contrarily to no-flow ischaemia. [9] The influence of metabolic substrates was also studied in LFI models induced by coronary stenosis in instrumented pig.…”