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1,25 Dihydroxyvitamin D-3 Inhibits TGF beta(1)-Mediated Primary Human Cardiac Myofibroblast Activation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
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2015 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 10, no 6Article in journal (Refereed) Published
Abstract [en]

Aims Epidemiological and interventional studies have suggested a protective role for vitamin D in cardiovascular disease, and basic research has implicated vitamin D as a potential inhibitor of fibrosis in a number of organ systems; yet little is known regarding direct effects of vitamin D on human cardiac cells. Given the critical role of fibrotic responses in end stage cardiac disease, we examined the effect of active vitamin D treatment on fibrotic responses in primary human adult ventricular cardiac fibroblasts (HCF-av), and investigated the relationship between circulating vitamin D (25(OH)D-3) and cardiac fibrosis in human myocardial samples. Methods and Results Interstitial cardiac fibrosis in end stage HF was evaluated by image analysis of picrosirius red stained myocardial sections. Serum 25(OH)D-3 levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)beta 1 to induce activation, in the presence or absence of active vitamin D (1,25(OH)(2)D-3). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)(2)D-3 treatment significantly inhibited TGF alpha 1-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25 (OH)(2)D-3. Treatment with 1,25(OH)(2)D-3 reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation. Conclusions Our results demonstrate that active vitamin D can prevent TGF beta 1-mediated biochemical and functional pro-fibrotic changes in human primary cardiac fibroblasts. An inverse relationship between vitamin D status and cardiac fibrosis in end stage heart failure was observed. Collectively, our data support an inhibitory role for vitamin D in cardiac fibrosis.

Place, publisher, year, edition, pages
2015. Vol. 10, no 6
National Category
Cardiac and Cardiovascular Systems
URN: urn:nbn:se:uu:diva-258777DOI: 10.1371/journal.pone.0128655ISI: 000355979500093PubMedID: 26061181OAI: diva2:842468
Available from: 2015-07-20 Created: 2015-07-20 Last updated: 2015-07-20Bibliographically approved

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