Publikasi Scopus 2010 s/d 2022

Introduction: Prolonged hyperglycaemia leads to several disadvantageous effects including hyperglycaemia-induced cardiac apoptosis in the diabetic cardiomyopathy. Previously, we have reported that olmesartan gave benefits in diabetic nephropathy by attenuating endoplasmic reticulum (ER) stress. However, the roles that olmesartan play in diabetic cardiomyopathy are not confirmed yet. Methods: The role of 6 weeks olmesartan medoxomil 10 mg/kg BW in the streptozotocin-induced C57/BL-6 mice were evaluated by measuring blood glucose level and body weight. Protein expression of glucose-regulated protein (GRP)-78 -an ER stress sensor-, cleaved caspase12 and C-EBP homologous protein (CHOP) -ER stress apoptosis initiating factors- were analysed using western blot. Cardiac apoptosis was measured by TUNEL staining. Results: GRP-78, caspase12 and CHOP protein expressions were significantly increased in the diabetic mice. Daily decoction of olmesartan for 6 weeks significantly reduced not only the ER stress chaperone GRP-78 but also the ER stress key initiating factors for apoptosis, caspase12 and CHOP. Constantly, diabetic mice receiving olmesartan suffered from lesser levels of cardiac apoptosis than diabetic mice receiving vehicle treatment. Conclusion: Olmesartan support a beneficial function in the diabetic cardiomyopathy not only by its original properties as an ARB but also as an ER stress inhibitor partly by inhibiting the initiation of pro-apoptotic pathway of GRP78/CHOP/caspase12. © 2022 UPM Press. All rights reserved.