title: Molecular and cellular mechanisms of aortic stenosis.
abstract: Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.
authors.affiliation: Department of Cardiology, University Hospital Maastricht, The Netherlands. e.yetkin@cardio.unimaas.nl
authors.forename: Ertan
authors.initials: E
authors.lastname: Yetkin
authors.forename: Johannes
authors.initials: J
authors.lastname: Waltenberger
mesh_terms: D001024:Aortic Valve Stenosis / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology*; D002114:Calcinosis / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D010006:Osteoblasts / Q000473:pathology*; D015995:Prevalence; D012307:Risk Factors