Vasonatrin peptide inhibits hypoxia-induced proliferation and collagen synthesis in cardiac fibroblasts

AIM To investigate the influence of vasonatrin peptide (VNP) on hypoxia induced proliferation and collagen synthesis in cultured cardiac fibroblasts (CFs) and the preventive mechanism of VNP in the interstitium remodeling of ischaemic heart diseases due to hypoxia. METHODS Neonatal rat CFs were obtained by enzymatic dissociation. Cell cycle kinetics of CFs was analyzed by flow cytometry. Collagen synthesis rate was determined by measuring 3H proline incorporation rate. RESULTS Hypoxia (20~30 mL·L -1 oxygen) alone for 24 h didn't change the cell cycle of cells cultured on serum free medium, but significantly increased the proliferation index [(S+G 2/M) / (S+G 2/M+G 0/G 1)] of CFs with low concentration serum (25 mL·L -1 ). VNP (10 -6 mol·L -1 ) inhibited the effects of hypoxia on low concentration serum induced proliferation ( P 0.01). Hypoxia increased basal (under nomoxide without serum) and low concentration serum induced collagen syntheses (under nomoxide with 25 mL·L -1 serum) by 19.6% ( P 0.05) and 37.2% ( P 0.01) in CFs, respectively. In a concentrate dependent manner, VNP (10 -8 ~10 -6 mol·L -1 ) decreased the incorporation of 3H proline induced by hypoxia for 24 h ( P 0.01). CONCLUSION Hypoxia might enhance serum induced proliferation in CFs and increase basal and serum induced collagen syntheses. VNP may attenuate myocardial fibrosis induced by hypoxia by inhibiting the above effects.