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Source: Thailand Medical News  Nov 30, 2019  5 years, 3 weeks, 11 hours, 16 minutes ago

HDAC9 Gene Identified As Playing Role In Hardening Of Blood Vessel Walls

HDAC9 Gene Identified As Playing Role In Hardening Of Blood Vessel Walls
Source: Thailand Medical News  Nov 30, 2019  5 years, 3 weeks, 11 hours, 16 minutes ago
Researchers from Massachusetts General Hospital have identified a specific gene, the HDAC9 gene in the calcification of the human aorta, the largest blood vessel in the body.

Typically, Cardiovascular Arterial wall calcification is the buildup of calcium in the blood vessel walls, which can often be a predictor of serious cardiovascular events like heart attacks and strokes. Scientists have long pointed to family history as one possible cause for this hardening of the arteries.


Genetics of blood vessel hardening. Credit: Mr. Haakon Sigurslid and Dr. Rajeev Malhotra


The new study was published in Nature Genetics journal.

The research study looked at more than 11,000 people and found patients with significant blood vessel calcification were more likely to have a specific variant of HDAC9. This high-risk variant of HDAC9 is present in about 25 percent of the population. In follow-up mouse studies, the researchers also found HDAC9 caused abnormal changes in the cells of the vessel walls, resembling that of human bone cells.

Dr Rajeev Malhotra, MD, of the Massachusetts General Hospital Cardiovascular Research Center and the study's co-lead author told Thailand Medical News, "Our research proved HDAC9 is not just associated with cardiovascular disease but can actually cause it by changing the makeup of those vascular cells. We then investigated it at the molecular level and looked at what would happen if we knocked out HDAC9."

The genetic researchers found that inhibiting HDAC9 in mice preserved normal function in vascular cells and prevented vascular calcification, therefore identifying HDAC9 as a target for the potential treatment of cardiovascular disease.  "Currently, there are no heart drugs available to patients that would prevent this type of hardening of the arteries," said Christopher J. O'Donnell, MD, MPH, of the Cardiology Divisions of Boston Veterans Administration Healthcare System and Brigham and Women's Hospital, and also a co-lead author of the study. "These findings are exciting in that they harness genetics to open the door for future pathways to heart disease prevention."

Reference: Rajeev Malhotra et al, HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype, Nature Genetics (2019). DOI: 10.1038/s41588-019-0514-8

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