Paricalcitol Attenuates Cardiac Fibrosis and Expression of Endothelial Cell Transition Markers in Isoproterenol-Induced Cardiomyopathic Rats

Objectives: Acute cardiomyopathy is a health problem worldwide. Few studies have shown an association between acute cardiomyopathy and low Vitamin D status. Paricalcitol, a Vitamin D receptor activator, clinically benefits patients with advanced kidney disease. The effect of paricalcitol supplement on cardiac remodeling in cardiomyopathic rats is unknown. This experimental study investigated the effect of paricalcitol in rats with cardiomyopathy induced by isoproterenol. Design: Prospective, randomized, controlled experimental study. Setting: Hospital-affiliated animal research institution. Subjects: Eight-week-old male Wistar-Kyoto rats. Interventions: Male Wistar-Kyoto rats were first injected intraperitoneally with isoproterenol to create a rat model of acute cardiomyopathy. Then paricalcitol was administered intraperitoneally to isoproterenol-injected rats at a dosage of 200 ng three times a week for 3 weeks. Relevant cardiomyopathy-related variables were measured regularly in three groups of rats, controls, isoproterenol, and isoproterenol plus paricalcitol. Rat hearts were obtained for evaluation of cardiac fibrosis using Masson trichrome staining and commercially available software, and evaluation of cell transition using immunofluorescence staining analysis. Measurements and Main Results: Isoproterenol infusions generated significant cardiac fibrosis (p < 0.001). Subsequent paricalcitol treatment attenuated the isoproterenol-induced cardiac fibrosis (p = 0.006). Fluorescence showed colocalization of endothelial and fibroblast cell markers (cluster differentiation 31 and -smooth muscle actin, respectively) in the isoproterenol-treated hearts. Paricalcitol injections attenuated the isoproterenol-induced fluorescence intensity of two cell markers (p < 0.01). Conclusions: Paricalcitol injections may ameliorate isoproterenol-induced cardiac fibrosis possibly through regulating cell transition.