1,25 Dihydroxyvitamin D3 Inhibits TGFβ1-Mediated Primary Human Cardiac Myofibroblast Activation.

Abstract

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)D3) 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)D3 levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)β1 to induce activation, in the presence or absence of active vitamin D (1,25(OH)2D3). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)2D3 treatment significantly inhibited TGFβ1-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation.

CONCLUSIONS:

Our results demonstrate that active vitamin D can prevent TGFβ1-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.

• Authors: Anna Meredith, Seti Boroomand, Jon Carthy, Zongshu Luo, Bruce McManus
• Journal: PloS one (PLoS One) Vol. 10 Issue 6 Pg. e0128655 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26061181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SMAD2 protein, human
• Smad2 Protein
• Transforming Growth Factor beta1
• Calcitriol

Topics

• Adult
• Calcitriol (pharmacology)
• Cells, Cultured
• Female
• Humans
• Male
• Middle Aged
• Myocytes, Cardiac (cytology, drug effects)
• Myofibroblasts (cytology, drug effects)
• Phosphorylation
• Smad2 Protein (metabolism)
• Transforming Growth Factor beta1 (physiology)