caa a22 4500 606158359 CHVBK 20210128100619.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10557-015-6629-y doi (NATIONALLICENCE)springer-10.1007/s10557-015-6629-y The Vitamin D Receptor Activator Maxacalcitol Provides Cardioprotective Effects in Diabetes Mellitus [Elektronische Daten] [Hideki Fujii, Kentaro Nakai, Yuriko Yonekura, Keiji Kono, Shunsuke Goto, Michinori Hirata, Masami Shinohara, Shinichi Nishi, Masafumi Fukagawa] Purpose: Recent reports showed a significant association between vitamin D levels and cardiovascular disease events and mortality. In the current study, we investigated the effect of the vitamin D receptor activator maxacalcitol (OCT) on cardiac damage in a rat model of type 2 diabetes. Methods: At 20 weeks of age, the rats were divided into three groups: vehicle-treated (DM), insulin-treated (INS) and OCT-treated (OCT). At 30 weeks, the rats were sacrificed and urinary and blood biochemical analyses and cardiac histological and immunohistochemical analyses were performed. To evaluate the effect of OCT on the renin-angiotensin system, we performed a further study using aliskiren (ALS). At 20 weeks, the diabetic rats were divided into two groups: the ALS-treated group (ALS) and the ALS plus OCT-treated group (ALS + OCT), and we evaluated the renin-angiotensin system (RAS) and cardiac lesions at 30 weeks. Results: At 30 weeks, despite comparable blood pressure and renal function, heart volume, intracardiac oxidative stress by immunohistological analysis, cardiac and perivascular fibrosis and urinary excretion of 8-hydroxydeoxyguanosine and serum N-terminal pro-brain natriuretic peptide levels were significantly decreased in the OCT group compared to the DM group. mRNA expressions of dihydronicotinamide adenine dinucleotide phosphate (NADPH) p47 subunit and cardiac injury-related markers in the heart were also significantly decreased in the OCT group compared to the DM group. The cardioprotective effect of OCT was preserved even in the context of RAS inhibition. Conclusion: Our results suggest that OCT prevents the development of cardiac damage in DM, independent of RAS inhibition. Springer Science+Business Media New York, 2015 Diabetes mellitus nationallicence Oxidative stress nationallicence Renin angiotensin system nationallicence Vitamin D receptor activator nationallicence Fujii Hideki Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut Nakai Kentaro Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut Yonekura Yuriko Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut Kono Keiji Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut Goto Shunsuke Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut Hirata Michinori Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd, Shizuoka, Japan aut Shinohara Masami Planning and Development Section, CLEA Japan, Inc, Tokyo, Japan aut Nishi Shinichi Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut Fukagawa Masafumi Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/6(2015-12-01), 499-507 0920-3206 29:6<499 2015 29 10557 https://doi.org/10.1007/s10557-015-6629-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10557-015-6629-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fujii Hideki Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut NATIONALLICENCE 700 1- Nakai Kentaro Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut NATIONALLICENCE 700 1- Yonekura Yuriko Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut NATIONALLICENCE 700 1- Kono Keiji Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut NATIONALLICENCE 700 1- Goto Shunsuke Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut NATIONALLICENCE 700 1- Hirata Michinori Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd, Shizuoka, Japan aut NATIONALLICENCE 700 1- Shinohara Masami Planning and Development Section, CLEA Japan, Inc, Tokyo, Japan aut NATIONALLICENCE 700 1- Nishi Shinichi Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut NATIONALLICENCE 700 1- Fukagawa Masafumi Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Hyogo, Japan aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/6(2015-12-01), 499-507 0920-3206 29:6<499 2015 29 10557