title: Early pathophysiological alterations in experimental cardiomyopathy: the Syrian cardiomyopathic hamster.
abstract: The Syrian cardiomyopathic hamster (SCH) is an established animal model for genetic cardiomyopathy. The disease in the hamster develops through similar stages to those observed in humans with this condition. The pathophysiological basis for this condition in the hamster resides in an inherited mutation in the gene encoding for delta-sarcoglycan, a component of the dystrophin complex. Two basic mechanisms contribute to cardiomyopathy in this model: ischemic heart disease by vasospasms of the coronary circulation and cardiomyocyte loss due to intrinsic cell defects. This review focuses on the etiology of vascular dysfunction and its role in the development of heart failure (HF) in this animal model. The data presented suggest that the vascular renin-angiotensin-system (RAS) plays a critical role in the generation of increased coronary reactivity and resistance in young SCH that have not yet developed the clinical manifestations of HF. The increased reactivity of the coronary vasculature results from endothelial dysfunction secondary to Ang II-dependent, oxidative stress. These alterations favor the development of ischemic heart disease and cardiomyopathy in adult animals. Indeed, RAS blockade during early stages of the disease significantly improves the clinical signs of dilated cardiomyopathy in this experimental model. These findings have significant implications for the prevention and treatment of cardiomyopathy in patients with ischemic heart disease, in particular, to those with familial sarcoglycanopathies.
authors.affiliation: Department of Physiology, University of Puerto Rico-School of Medicine, PO Box 365067 San Juan, Puerto Rico. nescobales@rcm.upr.edu
authors.forename: Nelson
authors.initials: N
authors.lastname: Escobales
authors.forename: María J
authors.initials: MJ
authors.lastname: Crespo
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000201:enzymology / Q000503:physiopathology*; D006224:Cricetinae; D004195:Disease Models, Animal; D007703:Peptidyl-Dipeptidase A / Q000502:physiology
chemical_list: D007703:Peptidyl-Dipeptidase A