Objectives: 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.
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.