Background: Cardiac failure, Cardiovascular diseases (CVD) including coronary artery, cerebrovascular and peripheral vascular disease are the leading causes of morbidity and mortality in both men and women, although female sex has long considered to be a “protective factor” against CVD. This study evaluated the effect of Selective estrogen receptor modulator (SERM) Raloxifene (RAL) therapy on endo-myocardium for therapeutic effectiveness in estrogen-depleted states induced by ovariectomy (OVX). Methods: We divided the rats into four groups: (I) Sham operated (II) ovariectomized controls without any treatment, (III) ovariectomized rats treated with vehicle sesame oil (IV) ovariectomized rats treated with raloxifene 1 mg/kg, s.c. daily for 60 days. Rats were sacrificed by transcardial perfusion. Different chambers of the heart sections were analyzed by image analysis software after hematoxylin and eosin staining. Results: This study reported that an increase in heart weight, cardiac wall thickness and myocytes diameter in response to estrogen depletion that can be effectively reversed by raloxifene treatment. Conclusion: This research revealed that the raloxifene treatment is the novel strategy to alleviate the post-menopausal problems and prevent the heart failure due to cardiac hypertrophy without the adverse effect of estrogen. This original article can give an idea to develop a cardioselective SERM`s which can be a used in both genders. The further studies are needed to find the molecular mechanisms of raloxifene over the hypo estrogenic cardiac myocytes
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