Grant: Project Grant

Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease. Although we can make a diagnosis of CAVS quite early we cannot treat this disorder with a medication. A 'wait and see approach' is used and when patients have a symptomatic severe CAVS they are referred for an open heart surgery. It is worth to point out that surgery is invasive and is associated with potential complications. Hence, the development of a medical therapy that would stop the disease process when diagnosed would obviate the need of a surgery. However, before we can develop novel medical therapies for CAVS further research is necessary in order to understand the molecular underpinnings of the disease process. We recently identified that a gene variant controlling the PALMD gene was involved in increasing the susceptibility to develop CAVS. We have identified that individuals that are carrier of this gene variant have less expression of PALMD in their aortic valves and ongoing work suggest that PALMD is an important regulator of valvular cellular function. A decreased level of PALMD promotes the thickening of the aortic valve. We will in the next several years investigate the role of PALMD during CAVS and we will also assess a novel therapy based on increasing PALMD level that we recently developed.