Enalaprilat exhibits anti-proliferative and anti-fibrotic effects on cardiac fibroblasts, likely mediated through the inhibition of TGF-β1 expression and antagonism of Angiotensin II.
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Hypothesis-generating in neonatal rat fibroblasts; leaves open translation to human cardiac fibrosis therapy.
The objectives of this study were to investigate the effects of the angiotensin I-converting enzyme inhibitor enalaprilat (Ena) on the proliferation, hydroxyproline content, and transforming growth factor β1 (TGF-β1) protein expression of neonatal cardiac fibroblasts and to probe its anti-cardiac fibrosis mechanism. Cardiac fibroblast (CFb) was isolated using the trypsin digestion method. Methyl thiazolyl tetrazolium (MTT) colorimetric assay was performed to evaluate cell proliferation, a hydroxyproline method of determination was used to measure collagen content, and reverse transcription-polymerase chain reaction and flow cytometry were used to detect mRNA TGF-β1 and protein levels, respectively, with Ena. Ena decreased dramatically the MTT value, the hydroxyproline content, and inhibited TGF-β1 transcription and protein expression in neonatal rat CFb. The antiproliferative effects of Ena on CFb may be attributed to the inhibition of TGF-β1 transcription and protein expression in cardiac fibroblasts and the antagonistic action of angiotensin II (Ang II).
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Du-Juan Yu (2012) studied this question.
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