HDAC9 in Vascular Calcification
Researchers here show that HDAC9 plays a role in the calcification of blood vessel walls, a process that contributes to the stiffening of blood vessels that leads to hypertension and all of the damage that chronic raised blood pressure causes to delicate tissues throughout the body. That mice lacking HDAC9 are more resistant to calcification suggests that there may be a mechanism here that can serve as the basis for a therapy to slow down the progression of calcification in human tissues. That said, it is worth comparing effort such as this with the potential for senolytic drugs to achieve similar results, based on the evidence for senescent cells to contribute to vascular calcification.
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. A new 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.
"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 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. These findings are exciting in that they harness genetics to open the door for future pathways to heart disease prevention."
Link: https://www.eurekalert.org/pub_releases/2019-10/mgh-sir102919.php