Altered sarcoplasmic reticulum Ca2+-ATPase gene expression in the human ventricle during end-stage heart failure

Abstract

A decrease in the myocardial level of the mRNA encoding the Ca2+-ATPase of the sarcoplasmic reticulum (SR) has been recently reported during experimental cardiac hypertrophy and failure. To determine if such a deficit occurs in human end-stage heart failure, we compared the SR Ca2+-ATPase mRNA levels in left (LV) and right ventricular (RV) specimens from 13 patients undergoing cardiac transplantation (6 idiopathic dilated cardiomyopathies; 4 coronary artery diseases with myocardial infarctions; 3 diverse etiologies) with control heart samples using a rat cardiac SR Ca2+-ATPase cDNA probe. We observed a marked decrease in the mRNA for the Ca2+-ATP-ase relative to both the 18S ribosomal RNA and the myosin heavy chain mRNA in LV specimens of patients with heart failure compared to controls (-48%, P < 0.01 and -47%, P < 0.05, respectively). The LV ratio of Ca2+-ATPase mRNA to 18S RNA positively correlated with cardiac index (P < 0.02). The RV ratio correlated negatively with systolic, diastolic and mean pulmonary arterial pressures (P < 0.02, P < 0.02, and P < 0.01, respectively). We suggest that a decrease of the SR Ca2+-ATPase mRNA in the myocardium plays an important role in alterations of Ca2+ movements and myocardial relaxation reported during human end-stage heart failure.