The Role of Endoplasmic Reticulum Stress in Calcific Aortic Valve Disease

Calcific aortic valve disease (CAVD), which is involved in osteogenic reprogramming of valvular interstitial cells, is the most common form of valve disease. It still lacks effective pharmacologic intervention, as its cellular biological mechanisms remain unclear. Congenital abnormality (bicuspid valve) and older age are considered to be the most powerful risk factors for CAVD. Aortic valve sclerosis (AVS) and calcific aortic stenosis (CAS), 2 subclinical forms of CAVD, represent 2 distinct stages of aortic valve calcification. During the AVS stage, the disease is characterised by endothelial activation/damage, inflammatory response, and lipid infiltration accompanied by microcalcification. The CAS stage is dominated by calcification, resulting in valvular dysfunction and severe obstruction to cardiac outflow, which is life threatening if surgery is not performed in time. Endoplasmic reticulum (ER) stress, a state in which conditions disrupting ER homeostasis cause an accumulation of unfolded and misfolded proteins in the ER lumen, has been shown to promote osteogenic differentiation and aortic valve calcification. Therefore, identifying targets or drugs for suppressing ER stress may be a novel approach for CAVD treatment.