Protective role of mast cells in homocysteine-induced cardiac remodeling

Recent reports including those from our laboratories indicate that hyperhomocysteinemia ( Hhe) is an independent risk factor for cardiac dysfunction and clinical heart failure. Mast cell accumulation is a prominent feature in our model of Hhe- induced cardiac dysfunction. Because mast cell- derived mediators can potentially attenuate cardiac remodeling, we investigated the possible protective role of mast cells in Hhe- induced cardiac remodeling using a mast cell- deficient rat model that in our recent report did not demonstrate any adverse cardiac function at younger age ( 6 mo) than mast cell- competent control animals. Mast cell- deficient ( Ws/ Ws) rats and mast cell- competent ( +/ +) littermate control animals ( 3 mo of age) were treated with a Hhe- inducing diet for 10 wk. Cardiac remodeling was assessed structurally utilizing histomorphometric methods and functionally using an isolated Langendorffperfused heart preparation. The Hhe- inducing diet caused similar elevations of homocysteine levels in the two groups. Compared with Hhe +/+ rats, the Hhe Ws/ Ws rats demonstrated strikingly exacerbated adverse cardiac remodeling and myocardial fibrosis. Cardiac function measurement showed worsened diastolic function in Hhe Ws/ Ws rats compared with Hhe +/+ rats. The absence of mast cells strikingly exacerbates Hhe- induced adverse cardiac remodeling and diastolic dysfunction. These findings indicate a potential dual rather than sole deleterious role for mast cells in cardiac injury.