Pathogenesis of Calcific Aortic Valve Disease

Abstract

Background-Over the past 10 to 15 years, calcific aortic valve disease, which includes aortic sclerosis and aortic stenosis, has come to be recognized as an active process, based on: (1) epidemiologic studies demonstrating associations of specific risk factors with increased prevalence or rate of progression of aortic valve disease; (2) identification, in valve lesions, of histopathologic features of chronic inflammation, lipoprotein deposition, renin-angiotensin system components, and molecular mediators of calcification; and (3) identification of cell-signaling pathways and genetic factors that may participate in valve disease pathogenesis. These studies will be reviewed and organized into a proposed global hypothesis for the pathogenesis of calcific aortic valve disease. Key Words: aortic valve disease Ⅲ calcification Ⅲ lipoproteins Ⅲ matrix Ⅲ angiotensin II C alcific aortic valve disease is identified by thickening and calcification of the aortic valve leaflets in the absence of rheumatic heart disease. It is divided, on a functional basis, into aortic sclerosis, in which the leaflets do not obstruct left ventricular outflow, and aortic stenosis, in which obstruction to left ventricular outflow is present. Aortic sclerosis is present in more than 25% of patients over age 65 1 and is associated with a 50% increase risk of cardiovascular events. 2 Aortic stenosis is present in 2% to 5% of very elderly patients, 1,3 is the second most common indication for cardiac surgery, 4 and carries an 80% 5-year risk of progression to heart failure, valve replacement, or death. 5 Though the disease is associated with substantial clinical consequences, there currently is no effective therapy for the disease other than surgical aortic valve replacement.The lack of medical therapies for calcific aortic valve disease can be traced to at least two important issues, one intellectual, the other practical. The first was the long-held notion that calcific aortic valve disease was a "degenerative," and therefore unmodifiable, condition. 6 However, more recent studies have demonstrated convincingly that calcific aortic valve lesions have many features characteristic of an active pathobiological process, including chronic inflammation, 7-9 lipoprotein deposition, 10 -12 active calcification, [13][14][15][16][17][18] and renin-angiotensin system activation. 19,20 These features are present in both trileaflet and bileaflet aortic valve lesions. 21 Also, an emerging body of literature is investigating how genetic factors might influence disease development. [22][23][24][25] The second issue is that, for many years, there were no animal models that faithfully replicated the key histological features of the disease. Recently, rabbit models been developed, 16,26,27 with that of Rajamannan and colleagues already providing a number of novel insights. 16 -18,28,29 In particular, these models have implicated the Wnt 18 and Runx2/ Cbfa1 16,17,27 signaling pathways in disease pathogenesis. Only very recently has a purported mouse model of calcif...

Prognostic factors for progression of early- and late-stage calcific aortic valve disease in Japanese: The Japanese Aortic Stenosis Study (JASS) Retrospective Analysis

“…6 Although several risk factors are shared between atherosclerotic diseases and CAVD, discrepancies in their pathogenesis have also been identified. [8][9][10] These results highlight the necessity of investigating prognostic factors for incidence and progression of CAVD in Asian populations.…”

Identification and Characterization of Aortic Valve Mesenchymal Progenitor Cells with Robust Osteogenic Calcification Potential

“…40 While some of the mechanisms involved in valve disease are similar to those in atherosclerosis, recent observations suggest anatomical, cellular, and genetic mechanisms that are unique to the aortic valve. 12,40,41 Accordingly, an improved understanding of the pathogenesis of calcific aortic valve disease requires better definition of these unique features, including the characteristics of the cell populations involved in the disease. In the present study, we identified for the first time a mesenchymal progenitor cell population in the aortic valve using rigorous quantitative assays established in the mesenchymal stem cell field.…”

Clinical approach to severe aortic stenosis with low flow and low gradient

“…[26,27] Bu nedenle, hastalar, sıklıkla aterosklerozun, arteriyel duvarda neden olduğu rijidite artışına bağlı gelişen, sistemik arteriyel kompliyansta azalma gibi bulgularına da sahiptirler.…”