The platelet: sensing shear and the endocrine regulation of cardiovascular sclerosis.

Abstract

Calcific aortic valve sclerosis (CAVS) causes profound morbidity in our increasingly dysmetabolic and aging citizenry.1 Two to five percent of our elderly population will require aortic valve replacement surgery to mitigate risk of death due to severe CAVS. Once considered only a passive process of dead and dying cells, arteriosclerotic calcification, including CAVS, has emerged as an actively regulated form of mineralized tissue metabolism.1 Preclinical and epidemiological studies reveal that aging; tobacco use; renal failure; bicuspid aortic valve; and the features of metabolic syndrome, hypertension, worsening glycemic control, hypertriglyceridemia, low high-density lipoprotein cholesterol, and obesity,2 are cumulative risk factors for arteriosclerotic valve calcification.1 Although hypercholesterolemia certainly contributes to risk of arteriosclerotic disease, targeting cholesterol via lipid-lowering statin therapy is insufficient to fully mitigate disease progression.1 Seminal histological studies by Otto et al3 indicate that although early valve lesions do exhibit intra- and extracellular lipid accumulation with inflammation, features of active matrix remodeling are present as well, including disruption of the elastic lamina with lamina fibrosa protein accumulation and microcalcification. With advanced disease, remodeling woven bone can be seen in ca. 13% of specimens4 although the molecular fingerprints of active osteogenesis are uniformly present even when amorphous calcium phosphate deposits predominate.1,4 Currently no medical therapies exist for preventing or treating CAVS, and our capacity to identify those at greatest risk for clinical progression is limited.1 In the Japanese Aortic Stenosis Study (JASS), although warfarin use portended worsening disease, treatment of hypertension with angiotensin receptor blockade was associated with attenuated risk of CAVS progression.5 …