title: Molecular and cellular aspects of calcific aortic valve disease.
abstract: Calcific aortic valve disease (CAVD) increasingly afflicts our aging population. One third of our elderly have echocardiographic or radiological evidence of calcific aortic valve sclerosis, an early and subclinical form of CAVD. Age, sex, tobacco use, hypercholesterolemia, hypertension, and type II diabetes mellitus all contribute to the risk of disease that has worldwide distribution. On progression to its most severe form, calcific aortic stenosis, CAVD becomes debilitating and devastating, and 2% of individuals >60 years are affected by calcific aortic stenosis to the extent that surgical intervention is required. No effective pharmacotherapies exist for treating those at risk for clinical progression. It is becoming increasingly apparent that a diverse spectrum of cellular and molecular mechanisms converge to regulate valvular calcium load; this is evidenced not only in histopathologic heterogeneity of CAVD, but also from the multiplicity of cell types that can participate in valve biomineralization. In this review, we highlight our current understanding of CAVD disease biology, emphasizing molecular and cellular aspects of its regulation. We end by pointing to important biological and clinical questions that must be answered to enable sophisticated disease staging and the development of new strategies to treat CAVD medically.
authors.affiliation: Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute at Lake Nona, Orlando, FL 32827, USA. dtowler@sanfordburnham.org
authors.forename: Dwight A
authors.initials: DA
authors.lastname: Towler
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology; D000082882:Bicuspid Aortic Valve Disease; D002114:Calcinosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006349:Heart Valve Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*
keywords: aortic valve, calcification of; vascular calcification; vascular senescence