Effect of fenofibrate on chymase-induced proliferation and collagen synthesis of rat cardiac fibroblast

AIM: To investigate the effect of fenofibrate on chymase-induced proliferation and collagen synthesis of rat cardiac fibroblasts (CFs). METHODS: Cultured CFs from neonatal Sprague Dawley rats were isolated and treated with chymase or together with fenofibrate. Cellular number and cycle were evaluated by MTT colorimetry (A490 value) and flow cytometry. The total collagen synthesis by CFs was examined by 3H-proline incorporation, and the expressions of mRNAs of types I and III collagen in CFs were determined by real-time PCR. RESULTS: MTT colorimetry showed that compared with those in control group, A490 increased to 0.42±0.05, whereas the value decreased to 0.35±0.06 (50 mg/L) and 0.28±0.05 (100 mg/L) in fenofibrate+cytometry group (P<0.05). The 3H-proline incorporations increased to 789±67 after chymase treatment; however, it significantly decreased with fenofibrate (P<0.05). Real-time PCR showed that mRNA levels of types I and III collagen in CFs were markedly upregulated by chymase (P<0.05), but fenofibrate inhibited the upregulation (P<0.05). Cellular cycle analysis showed that chymase markedly decreased cellular percentage in G0/G1 stage and increased cellular percentage in S stage and proliferation index (PI), which were significantly attenuated by fenofibrate (P<0.05). CONCLUSION: PPARα agonist fenofibrate inhibits chymase-induced proliferation and collagen synthesis of rat CFs, which is probably a potential way to attenuate myocardial fibrosis.