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Publication : HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

First Author	Malhotra R	Year	2019
Journal	Nat Genet	Volume	51
Issue	11	Pages	1580-1587
PubMed ID	31659325	Mgi Jnum	J:282483
Mgi Id	MGI:6381020	Doi	10.1038/s41588-019-0514-8
Citation	Malhotra R, et al. (2019) HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype. Nat Genet 51(11):1580-1587

abstractText

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 x 10(-8)). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.

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