Reduced myocardial nerve growth factor expression in human and experimental heart failure

Maintenance of cardiac performance is tightly controlled by the autonomic n ervous system. In congestive heart failure (CHF), although the adverse path ophysiological effects of cardiac sympathetic overactivity are increasingly recognized, the paradoxical finding of reduced sympathetic innervation den sity in the failing heart remains unexplained. Given these observations, we tested the hypothesis that a reduction in the myocardial production of ner ve growth factor (NGF), which is important for the maintenance of sympathet ic neuronal survival, could explain the conflicting neurochemical and neuro anatomical profile of CHF. In healthy humans (n=11), there was a significan tly greater transcardiac venoarterial plasma NGF gradient than in CHF patie nts (n=11, P<0.05). In a rat model of CHF, a 40% reduction (P<0.05) NGF mRN A expression was apparent in association with a 24% reduction in tissue NGF content (P<0.05). In conjunction, evidence of reduced sympathetic innervat ion in the failing heart was apparent, as measured histologically by catech olamine fluorescence and by expression of the neuronal NGF receptor trkA. N orepinephrine (10 mu mol/L) exposure reduced both NGF mRNA and protein expr ession in isolated cardiomyocytes, suggesting that myocardial NGF downregul ation may represent an adaptive response to sympathetic overactivity. These data indicate that NGF expression in the heart is dynamic and may be alter ed in cardiovascular disease states. In CHF, reduced NGF expression may acc ount for alterations in sympathetic neuronal function and neuroanatomy. The full text of this article is available at http://www.circresaha.org.