Abnormal gene expression of cardiac fibroblasts in experimental aortic regurgitation.

Abstract

Extensive primary fibrosis precedes heart failure and death in experimental chronic aortic regurgitation. To seek the molecular basis for this observation, this study analyzed the RNA pool for genes that are up-or downregulated in aortic regurgitation fibroblasts. Differential display reverse transcriptase polymerase chain reaction was used to compare RNA extracted from cardiac fibroblasts isolated from three healthy New Zealand white rabbits and from three with aortic regurgitation. Using two base anchoring oligo d(T) primers (T11VN) together with arbitrary upstream primers, numerous differences in normal versus aortic regurgitation gene expression were apparent on differential display reverse transcriptase polymerase chain reaction. The aortic regurgitation cell cultures showed numerous differentially up-and downregulated genes compared with cell cultures of normal cardiac fibroblasts. The results showed that pathologic fibrosis in chronic experimental aortic regurgitation is associated with abnormal cardiac fibroblast gene expression, which may be pathogenic for the fibrous lesion.