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 Langendorff-perfused 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.
Joseph
Jacob
J
Department of Internal Medicine, Veterans Affairs Boston Healthcare System, and Boston University School of Medicine, Boston, Massachusetts, USA. jacob.joseph@med.va.gov
Kennedy
Richard H
RH
Devi
Sulochana
S
Wang
Junru
J
Joseph
Lija
L
Hauer-Jensen
Martin
M
D000818:Animals; D003971:Diastole / Q000502:physiology; D005355:Fibrosis; D006331:Heart Diseases / Q000473:pathology / Q000503:physiopathology*; D006710:Homocysteine / Q000502:physiology*; D020138:Hyperhomocysteinemia / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008407:Mast Cells / Q000502:physiology*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011922:Rats, Mutant Strains; D020257:Ventricular Remodeling / Q000502:physiology*
D006710:Homocysteine