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Cardiovascular disease is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM), and patients with DM frequently develop diabetic cardiomyopathy. Currently, effective treatments for diabetic cardiomyopathy are limited. Vitamin D exerts pleiotropic effects on the cardiovascular system and is associated with DM. The purpose of this review was to evaluate published research on vitamin D in diabetic cardiomyopathy by searching PubMed databases. Herein, we reviewed vitamin D metabolism; evaluated the molecular, cellular, and neuroendocrine effects in native and bioactive vitamin D; and evaluated the role of vitamin D in treating cardiovascular disease and DM. Some evidence suggests that vitamin D may improve cardiovascular outcomes in diabetes through anti-inflammatory, antioxidative, antihypertrophic, antifibrotic, and antiatherosclerotic activities and by regulating advanced glycation end-product signaling, the renin-angiotensin system, and cardiac metabolism. This clinical and laboratory evidence suggests that vitamin D may be a potential agent in treating diabetic cardiomyopathy. However, using vitamin D entails possible adverse risks of hypercalcemia, hyperphosphatemia, and vascular calcifications. Therefore, future studies should be conducted that clarify the potential benefits of vitamin D through large-scale randomized clinical trials in well-defined groups of diabetic patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Receptor for advanced glycation end products (RAGE) signaling pathway plays a vital role in diabetic cardiovascular complications. Calcitriol has been shown to exert various beneficial cardiovascular effects. The purpose of this study is to determine whether calcitriol can modulate RAGE expression, and study the potential mechanisms in diabetic hearts. Methods: Streptozotocin (65mg/kg, intraperitoneal injection once) induced diabetic rats were treated with or without subcutaneous injections of calcitriol at a dose of 150ng/kg/day for 4weeks. Western blot was used to evaluate protein expressions of myocardial RAGE, TNF-α, p65 subunit of NF-κB (p65), α subunit of inhibitor of κB (IκBα), subunits of NADPH oxidase (NOX4 and p22phox), angiotensin II type 1 receptor (AT1R), TGF-β1, TGF-β receptor I, total and phosphorylated SMAD2/3 and ERK, matrix metalloproteinases 2 (MMP2), tissue inhibitors of metalloproteinases 2 (TIMP2) and procollagen I. Results: As compared to control, diabetic rats had increased expressions of cardiac RAGE, TNF-α, p22phox, AT1R, and TGF-β1, which were significantly attenuated in the diabetic rats treated with calcitriol. Calcitriol-treated diabetic hearts also had lesser expressions of p-SMAD2/3 and p-ERK signaling than those of diabetic hearts. Moreover, diabetic hearts had increased expressions of MMP2 and procollagen I and decreased TIMP2. However, calcitriol reverted the diabetic effects in procollagen I but not in MMP2 or TIMP2. Conclusions: Calcitriol decreased diabetic effects on RAGE and fibrosis, which may be caused by its modulation on AT1R and the anti-inflammatory and antioxidative potentials. Therefore, calcitriol may attenuate diabetic cardiomyopathy. [Copyright &y& Elsevier]