title: The Vitamin D Receptor Activator Maxacalcitol Provides Cardioprotective Effects in Diabetes Mellitus.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our results suggest that OCT prevents the development of cardiac damage in DM, independent of RAS inhibition.
authors.affiliation: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. fhideki@med.kobe-u.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakai
authors.affiliation: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Yonekura
authors.affiliation: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Kono
authors.affiliation: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Goto
authors.affiliation: Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd, Shizuoka, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Hirata
authors.affiliation: Planning and Development Section, CLEA Japan, Inc, Tokyo, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishi
authors.affiliation: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.|Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
keywords: Diabetes mellitus; Oxidative stress; Renin angiotensin system; Vitamin D receptor activator