title: 1,25-Dihydroxyvitamin-D3 treatment reduces cardiac hypertrophy and left ventricular diameter in spontaneously hypertensive heart failure-prone (cp/+) rats independent of changes in serum leptin.
abstract: A number of investigators have observed insufficient 25-hydroxyvitamin D status in patients with congestive heart failure, suggesting a role for vitamin D insufficiency in the pathogenesis of this disorder. We have observed cardiac hypertrophy and collagen accumulation in rats deficient in vitamin D and in the hearts of vitamin D-receptor knockout mice. Our studies indicate that absence of vitamin D-mediated signal transduction and genomic activation results in cardiomyocytes overstimulation including increased contractility. These events ultimately lead to cardiomyocyte hypertrophy. In this report, we used spontaneously hypertensive heart failure rats cp/+ (hemyzygous for the corpulent gene, a mutant isoform of the leptin receptor) fed a normal and a high-salt diet to assess the potential for activated vitamin D (1,25 dihydroxyvitamin D3) to prevent cardiac hypertrophy and increases in cardiac output. After 13 weeks, as compared with untreated rats, we observed that 1,25 dihydroxyvitamin D3 treatment in rats fed a high-salt diet resulted in lower heart weight, myocardial collagen levels, left ventricular diameter, and cardiac output despite higher serum leptin levels. These studies suggest that 1,25(OH)2D3 treatment may prevent the development of cardiac hypertrophy, an important contributing factor in the progression of congestive heart failure.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Mancuso
authors.forename: Ayesha
authors.initials: A
authors.lastname: Rahman
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hershey
authors.forename: Loredana
authors.initials: L
authors.lastname: Dandu
authors.forename: Karl A
authors.initials: KA
authors.lastname: Nibbelink
authors.forename: Robert U
authors.initials: RU
authors.lastname: Simpson
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002302:Cardiac Output; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000235:genetics; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000097:blood*; D008274:Magnesium / Q000097:blood; D008297:Male; D009154:Mutation; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D010710:Phosphates / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D054411:Receptors, Leptin / Q000235:genetics; D013977:Tibia / Q000473:pathology; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D020738:Leptin; D010710:Phosphates; D054411:Receptors, Leptin; D014815:Vitamins; D003094:Collagen; D002117:Calcitriol; D008274:Magnesium; D002118:Calcium