Abstract
Cyclosporine A has been implicated in the pathogenesis of myocardial interstitial fibrosis observed in heart transplant recipients. However, other confounding variables such as posttransplantation hypertension and rejection episodes may also be responsible for interstitial fibrosis development and associated abnormalities in ventricular diastolic function. Therefore, we examined whether cyclosporine A directly or indirectly affects fibrillar collagen metabolism by cardiac fibroblasts in vitro. Rat cardiac fibroblasts were isolated by collagenase digestion. Subconfluent cultures were then maintained (24 hours) in serum-containing or serum-free medium before addition of cyclosporine A (50-1,000 ng/mL). After an additional 24 hours, total procollagen synthesis, accumulation, and degradation were analyzed by measuring hydroxyproline content in the cell monolayer and in the ethanol-soluble and ethanol-precipitable fractions of the culture medium. mRNA levels for alpha 1(I) and alpha 1(III) procollagen polypeptides were assessed 2, 6, 12, and 24 hours after cyclosporine A treatment using Northern blot analysis. The results were compared with control cultures maintained in the absence of cyclosporine A. There were no differences in pr...Continue Reading
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