|Increased dietary intake of vitamin A promotes aortic valve calcification in vivo.|
|PMID: 23202364 Owner: NLM Status: MEDLINE|
|OBJECTIVE: Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo and examined the molecular mechanisms of RA signaling during the calcification process in vitro.
METHODS AND RESULTS: Using a combination of approaches, we defined calcific aortic valve disease pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular, and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated Sox9 repression and calcification is regulated by classical RA signaling and requires both RA and retinoid X receptors.
CONCLUSIONS: Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of calcific aortic valve disease in the human population.
|Danielle J Huk; Harriet L Hammond; Hiroyuki Kegechika; Joy Lincoln|
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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-11-29|
|Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 33 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2013 Feb|
|Created Date: 2013-01-17 Completed Date: 2013-03-14 Revised Date: 2014-02-04|
Medline Journal Info:
|Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States|
|Languages: eng Pagination: 285-93 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Aortic Valve / metabolism*, pathology
Calcinosis / etiology*, genetics, metabolism, pathology
Collagen Type II / genetics, metabolism
Disease Models, Animal
Gene Expression Profiling / methods
Gene Expression Regulation
Heart Valve Diseases / etiology*, genetics, metabolism, pathology
Hypervitaminosis A / chemically induced, complications*, genetics, metabolism, pathology
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
Osteogenesis / genetics
Osteopontin / genetics, metabolism
Receptors, Retinoic Acid / genetics, metabolism
Retinoid X Receptors / genetics, metabolism
SOX9 Transcription Factor / genetics, metabolism
Tissue Culture Techniques
Tretinoin / metabolism
Vitamin A / analogs & derivatives*, metabolism
Vitamins* / metabolism
|R01 HL091878/HL/NHLBI NIH HHS; R01-HL091878/HL/NHLBI NIH HHS|
|0/Collagen Type II; 0/Receptors, Retinoic Acid; 0/Retinoid X Receptors; 0/SOX9 Transcription Factor; 0/Vitamins; 106441-73-0/Osteopontin; 11103-57-4/Vitamin A; 1D1K0N0VVC/retinol palmitate; 5688UTC01R/Tretinoin|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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