SUBJECTS AND METHODS: The pattern of gene expression was studied, using a cDNA microarray, in myocardium from 4 normal subjects and 5 patients with chronic regurgitant valvular heart disease whose end-diastolic left ventricular dimension measures 65 mm or more, but whose systolic function remained preserved.

RESULTS: We identified 58 differentially expressed genes that were functionally classifiable in the volume-overloaded myocardium. Those genes involved in cell cycle/growth (up/down-regulation: 9/1), signal transduction (4/1) were mostly overexpressed in the volume-overloaded myocardium. The distributions of the gene expressions were variable for those involved in transcription/translation (up/down-regulation: 6/7) and apoptosis (2/2). The genes related to the myocyte structure (troponin T3, tropomyosin, etc)(up/down-regulation: 1/10), as well as those related to metabolism (2/5), were underexpressed. The gene expression patterns from RT-PCR and Western blot, with randomly selected genes, were similar to those from the cDNA microarray.

CONCLUSION: Altered expression was identified in multiple genes in the volume-overloaded human left ventricle prior to the development of heart failure. The genes related to cell growth and signal transduction were mostly overexpressed, while those related to cellular structure and metabolism appeared to be underexpressed. These results might help in the elucidation of cellular mechanisms for the remodeling process associated with chronic volume-overloading.