Excess vitamin A intake has calcification repercussions

Excess dietary vitamin A intake is significantly associated with increased heart valve calcification, show results from an animal study.

This finding suggests that hypervitaminosis A could be a new risk factor for calcific aortic valve disease in the human population, write Joy Lincoln (Nationwide Children's Hospital, Columbus, Ohio, USA) and team in Arteriosclerosis, Thrombosis and Vascular Biology.

They identified that mice who were fed 200 IU/g of retinyl palmitate for 12 months developed significantly greater aortic valve stenosis and leaflet calcification compared with those fed 20 IU/g.

The authors say that the increased aortic valve stenosis seen in mice fed excess vitamin A is attributed to the formation of calcific nodules on the cusp surface and increased expression of osteogenic genes, as commonly observed in human patients with calcific aortic valve disease.

This suggests that high retinoid exposure is detrimental to heart valve structure and function in mice, they explain.

Using an in vitro valve explants culture system, the researchers show that retinoic acid-mediated Sox9 repression and calcification is regulated by classical retinoic acid signaling and requires both retinoic acid and retinoid X receptors.

"These results imply that retinoic acid signaling must be tightly regulated in adult mice to maintain heart valve connective tissue homeostasis," write the authors.

"Findings from this study suggest that excess exposure to retinoids could contribute to calcific aortic valve disease onset and progression in the human population."

Lincoln and team point out that, although hypervitaminosis A induced by dietary intake is not highly prevalent in developed countries, high retinol levels are more common in individuals ingesting dietary supplements or in patients receiving retinol-based pharmaceuticals.

"On the basis of this current study retinol levels predicting calcific aortic valve disease susceptibility could improve risk stratification and help determine a therapeutic window to improve patient outcome," the researchers conclude.

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