Role of Intra‐cardiac Neurohumoral Factors in Human Chronic Ischemic Heart Disease

Abstract

BackgroundA transient myocardial ischemia results in the destruction of typical metabolic cascades and leaves structural “traces” in the cardiomyocytes and myocardial interstitial components. Those structural “traces” are microscopically determined by disseminated micro‐focal alterations of the ultrastructure of the cardiomyocytes along with increased interstitial fibrosis. However, cardiac sympathetic nerve terminals are more sensitive to transient myocardial ischemia than the cardiomyocytes. The present study performed ultramicroscopic characterizations of sympathetic nerve terminals in human ischemic heart disease.MethodsLeft ventricular myocardial biopsies were taken from patients with chronic ischemic heart disease and examined under transmission electron microscopy (TEM) using the electron‐histochemical method. Ultrastructural details of alterations in cardiac sympathetic nerve terminals were analyzed to assess their role in the fibrosis development and the damage to cardiomyocytes.ResultsIn patients, the decrease in vesicles of sympathetic nerve terminals and the polymorphism of their secretory granules indicate decreased neo‐synthesis of neurotransmitters as well as their up‐take. We also found that glycocalyx is dissociated and micro‐configurated and cell membranes are lysed. These structural observations imply that the neurotransmitter release into the peri‐cellular space activates functions of mast cells, endothelial cells, fibroblasts, contributing to cardiomyocyte damage and the development of myocardial fibrosis.ConclusionThese results suggest that the accumulation of endogenous cardiac neurotransmitters in the myocardial interstitium may lead to the progressive damage to cardiomyocytes and the development of cardiac fibrosis in human ischemic heart disease. Understanding mechanisms of the regulation of endogenous cardiac neurohumoral factors, especially those involved in the initiation, progression and resolution of cardiac fibrosis is crucial to prevent the ventricular cardiomyocyte damage and to design anti‐fibrosis treatment strategies for patients with chronic ischemic heart disease.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.