کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2525172 1119599 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthetic prostacycline agonist, ONO-1301, ameliorates left ventricular dysfunction and cardiac fibrosis in cardiomyopathic hamsters
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی تومور شناسی
پیش نمایش صفحه اول مقاله
Synthetic prostacycline agonist, ONO-1301, ameliorates left ventricular dysfunction and cardiac fibrosis in cardiomyopathic hamsters
چکیده انگلیسی

Impairment of cardiac function in cardiomyopathy has been postulated to be related to decreased blood flow and increased collagen synthesis. Administration of growth factors was reported to attenuate left ventricular (LV) remodeling and dysfunction in animal models of dilated cardiomyopathy. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor and vascular endothelial growth factor from various cell types and ameliorate ischemia-induced LV dysfunction in mice and pigs. We evaluated therapeutic efficacy of ONO-1301 in the Syrian hamster (TO-2), a model of genetically determined dilated cardiomyopathy. Either vehicle or a slow releasing form of ONO-1301 (ONO-1301-PLGA, 10 mg/kg/3 weeks) was administered subcutaneously every 3 weeks to TO-2 hamsters from 24 to 32 weeks of age (n = 12 for each group). Age-matched F1B hamsters were used as a control. Plasma concentration of HGF was elevated in ONO-1301-PLGA group (p < 0.05). Echocardiographic study demonstrated that LV fractional shortening was significantly improved in the ONO-1301-PLGA group (25 ± 4%, p < 0.01) compared with that in the vehicle group (19 ± 2%). Cardiac fibrosis was significantly reduced by ONO-1301-PLGA (p < 0.05) as determined by Azan-Mallory staining. Capillary density of left ventricle was markedly reduced in TO-2 hamsters. ONO-1301-PLGA significantly increased capillary density in TO-2 group (p < 0.05). ONO-1301 improved LV dysfunction and reduced cardiac fibrosis in the hamster model of dilated cardiomyopathy. ONO-1301 might hold a therapeutic potential in the treatment of dilated cardiomyopathy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomedicine & Pharmacotherapy - Volume 63, Issue 10, December 2009, Pages 781–786
نویسندگان
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