1,25-Dihydroxyvitamin D3 receptors identified in the rat heart

Walters, Marian R.; Wicker, Donna Cuneo; Riggle, Paul C.

doi:10.1016/s0022-2828(86)80983-x

Cited by 110 publications

(70 citation statements)

References 19 publications

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“…Skin-derived 7-dehydrocholesterol undergoes liver hydroxylation to form 25(OH)D 3 , the storage form of vitamin D (21). The kidney hydroxylates 25(OH)D 3 to 1,25(OH) 2 D 3 , the active form of vitamin D that exerts its effect through binding the nuclear VDR present in cells, including smooth muscle and endothelial cells, and possibly cardiomyocytes (7,22,23). A 25(OH)D 3 deficiency leads to derangements in cardiac myocyte contraction (24), proliferation (25), and cardiac collagen accumulation (26).…”

Section: Discussionmentioning

confidence: 99%

Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Bodyak

Ayus²,

Achinger³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

304

250

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Observations in hemodialysis patients suggest a survival advantage associated with activated vitamin D therapy. Left ventricular (LV) structural and functional abnormalities are strongly linked with hemodialysis mortality. Here, we investigated whether paricalcitol (PC, 19-nor-1,25(OH)2D2), an activated vitamin D compound, attenuates the development of LV abnormalities in the Dahl salt-sensitive (DSS) rat and whether humans demonstrate comparable findings. Compared with DSS rats fed a high-salt (HS) diet (6% NaCl for 6 weeks), HS؉PC was associated with lower heart and lung weights, reduced LV mass, posterior wall thickness and end diastolic pressures, and increased fractional shortening. Blood pressures did not significantly differ between the HS groups. Plasma brain natriuretic peptide levels, and cardiac mRNA expression of brain natriuretic peptide, atrial natriuretic factor, and renin were significantly reduced in the HS؉PC animals. Microarray analyses revealed 45 specific HS genes modified by PC. In a retrospective pilot study of hemodialysis patients, PC-treated subjects demonstrated improved diastolic function and a reduction in LV septal and posterior wall thickness by echocardiography compared with untreated patients. In summary, PC attenuates the development of LV alterations in DSS rats, and these effects should be examined in human clinical trials.cardiac hypertrophy ͉ heart failure ͉ paricalcitol ͉ renal failure T he rate of cardiovascular-related mortality in hemodialysis patients is 10-20 times higher than that observed in the general population (1). Left ventricular hypertrophy (LVH) and diastolic dysfunction are present in Ͼ50% of patients at dialysis initiation, and these abnormalities are strongly linked with dialysis-related mortality (2). Currently, there are no well accepted means to modify cardiac structural and functional alterations in renal-failure patients.We recently demonstrated in observational studies that therapy with activated vitamin D to chronic hemodialysis patients is associated with reduction in cardiovascular-related mortality (3, 4). Conversion of nutritional vitamin D (25(OH)D 3 ) to the hormonally active form of vitamin D (1,25(OH) 2 D 3 ) occurs primarily in the kidney; thus, patients with kidney failure commonly present with altered vitamin D status (5). There is growing evidence that vitamin D either directly or indirectly affects cardiac structure and function. The vitamin D receptor knockout mouse model demonstrates increased cardiac renin expression and marked cardiomyocyte hypertrophy (6), and 1,25(OH) 2 D 3 attenuates cardiomyocyte proliferation (7) and hypertrophy (8) in vitro. Here, we demonstrate that treatment with an activated vitamin D compound attenuates the development of cardiac hypertrophy and dysfunction in a recognized animal model of such abnormalities and that comparable findings are evident in humans.

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Section: Discussionmentioning

confidence: 99%

Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Bodyak

Ayus²,

Achinger³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

304

250

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“…Several studies have shown that cardiac myocytes express a functional VDR, which is primarily located in the nucleus and within, or adjacent to the t-tubules [5][6][7][8][9][10][11]. Cardiac fibroblasts also express the VDR.…”

Section: Myocardial Vdr Expression and Metabolismmentioning

confidence: 99%

Vitamin D deficiency and myocardial diseases

Pilz

Tomaschitz

Drechsler

et al. 2010

Molecular Nutrition Food Res

135

142

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Vitamin D deficiency is common among patients with myocardial diseases because sun-induced vitamin D production in the skin and dietary intake of vitamin D is often insufficient. Knockout mice for the vitamin D receptor develop myocardial hypertrophy and dysfunction. It has also been shown that children with rickets who suffered from severe heart failure could be successfully treated with supplementation of vitamin D plus calcium. In adults, almost all patients with heart failure exhibit reduced 25-hydroxyvitamin D levels, which are used to classify the vitamin D status. In prospective studies, vitamin D deficiency was an independent risk factor for mortality, deaths due to heart failure and sudden cardiac death. Several vitamin D effects on the electrophysiology, contractility, and structure of the heart suggest that vitamin D deficiency might be a causal factor for myocardial diseases. Data from interventional trials, however, are rare and urgently needed to elucidate whether vitamin D supplementation is useful for the treatment of myocardial diseases. In our opinion, the current knowledge of the beneficial effects of vitamin D on myocardial and overall health strongly argue for vitamin D supplementation in all vitamin D-deficient patients with or at high risk for myocardial diseases.

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“…2 Apart from playing a recognized role in suppressing secondary hyperparathyroidism, vitamin D has been suggested to play a protective role against cardiovascular disease and exert its effects on the heart and vascular walls through interaction with the vitamin D receptor. 3,4 Experimental studies showed associations between vitamin D deficiency and impairment of cardiac contractile function, 5 increased myocardial collagen content, and increased cardiac mass. 6,7 Similarly, targeted deletion of the vitamin D receptor gene resulted in increased cardiomyocyte size and LV weight.…”

mentioning

confidence: 99%

Effect of Paricalcitol on Left Ventricular Mass and Function in CKD—The OPERA Trial

Wang

Fang

Chan

et al. 2014

Journal of the American Society of Nephrology

224

192

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Vitamin D seems to protect against cardiovascular disease, but the reported effects of vitamin D on patient outcomes in CKD are controversial. We conducted a prospective, double blind, randomized, placebocontrolled trial to determine whether oral activated vitamin D reduces left ventricular (LV) mass in patients with stages 3-5 CKD with LV hypertrophy. Subjects with echocardiographic criteria of LV hypertrophy were randomly assigned to receive either oral paricalcitol (1 mg) one time daily (n=30) or matching placebo (n=30) for 52 weeks. The primary end point was change in LV mass index over 52 weeks, which was measured by cardiac magnetic resonance imaging. early diastolic and systolic mitral annular velocities, and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups. However, paricalcitol treatment significantly reduced intact parathyroid hormone (P,0.001) and alkaline phosphatase (P=0.001) levels as well as the number of cardiovascular-related hospitalizations compared with placebo. In conclusion, 52 weeks of treatment with oral paricalcitol (1 mg one time daily) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD.

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1,25-Dihydroxyvitamin D3 receptors identified in the rat heart

Cited by 110 publications

References 19 publications

Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Vitamin D deficiency and myocardial diseases

Effect of Paricalcitol on Left Ventricular Mass and Function in CKD—The OPERA Trial

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