Increased Level of Pericardial Insulin-Like Growth Factor-1 in Patients With Left Ventricular Dysfunction and Advanced Heart Failure

Abstract

To test the hypothesis that the cardiac insulin-like growth factor-1 (IGF-1) system is up-regulated in the failing heart, we measured the pericardial (cardiac) and plasma (circulating) IGF-1 levels in coronary artery disease patients. Local IGF-1 systems are regulated differently from the systemic IGF-1 system. The cardiac IGF-1 system is up-regulated by the increased left ventricular (LV) wall stress. However, it remains unknown how this system is affected in LV dysfunction and heart failure. We measured the plasma and pericardial fluid levels of IGF-1 and brain natriuretic peptide (BNP) in 87 coronary artery disease patients undergoing cardiac surgery, and examined their relationships with LV function and heart failure severity. The expressions of IGF-1 and IGF-1 receptor proteins were examined in endomyocardial biopsies obtained from other patients with normal or impaired LV function. The pericardial IGF-1 and BNP levels were positively correlated with the plasma BNP level (both p < 0.001). The pericardial IGF-1 level was increased in heart failure patients, whereas the plasma IGF-1 level was rather decreased. The pericardial IGF-1 level was inversely correlated with the LV ejection fraction (p < 0.001), whereas the plasma IGF-1 level was not. Positive immunostaining for IGF-1 and IGF-1 receptor proteins was enhanced in myocardial biopsies from failing hearts compared with those from nonfailing hearts. The pericardial IGF-1 level was increased in patients with LV dysfunction and heart failure, whereas the plasma IGF-1 level was decreased. These results may indicate that up-regulation of the cardiac IGF-1 system serves as a compensatory mechanism for LV dysfunction.