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Differential expression of cartilage and bone-related proteins in pediatric and adult diseased aortic valves.

ABSTRACT: Approximately 5 million people are affected with aortic valve disease (AoVD) in the United States. The most common treatment is aortic valve (AoV) replacement surgery, however, replacement valves are susceptible to failure, necessitating additional surgeries. The molecular mechanisms underlying disease progression and late AoV calcification are not well understood. Recent studies suggest that genes involved in bone and cartilage development play an active role in osteogenic-like calcification in human calcific AoVD (CAVD). In an effort to define the molecular pathways involved in AoVD progression and calcification, expression of markers of valve mesenchymal progenitors, chondrogenic precursors, and osteogenic differentiation was compared in pediatric non-calcified and adult calcified AoV specimens. Valvular interstitial cell (VIC) activation, extracellular matrix (ECM) disorganization, and markers of valve mesenchymal and skeletal chondrogenic progenitor cells were observed in both pediatric and adult AoVD. However, activated BMP signaling, increased expression of cartilage and bone-type collagens, and increased expression of the osteogenic marker Runx2 are observed in adult diseased AoVs. They are not observed in the majority of pediatric diseased valves, representing a marked distinction in the molecular profile between pediatric and adult diseased AoVs. The combined evidence suggests that an actively regulated osteochondrogenic disease process underlies the pathological changes affecting AoVD progression, ultimately resulting in stenotic AoVD. Both pediatric and adult diseased AoVs express protein markers of valve mesenchymal and chondrogenic progenitor cells while adult diseased AoVs also express proteins involved in osteogenic calcification. These findings provide specific molecular indicators of AoVD progression, which may lead to identification of early disease markers and the development of potential therapeutics.

SUBMITTER: Wirrig EE

PROVIDER: S-EPMC3035730 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Differential expression of cartilage and bone-related proteins in pediatric and adult diseased aortic valves.

Wirrig Elaine E EE Hinton Robert B RB Yutzey Katherine E KE

Journal of molecular and cellular cardiology 20101214 3

Approximately 5 million people are affected with aortic valve disease (AoVD) in the United States. The most common treatment is aortic valve (AoV) replacement surgery, however, replacement valves are susceptible to failure, necessitating additional surgeries. The molecular mechanisms underlying disease progression and late AoV calcification are not well understood. Recent studies suggest that genes involved in bone and cartilage development play an active role in osteogenic-like calcification in ...[more]

PMID: 21163264

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Project description:BackgroundThe durability of transcatheter aortic valves (TAVs) remains their greatest disadvantage, given that fixed tissue leaflets are not immune to structural degeneration from calcification and thrombosis. Therefore, a second intervention is necessary, especially given that TAV in low-risk patients has shown noninferior outcomes compared with surgery. This study aimed to assess the hemodynamic and turbulent properties of the flow downstream with different TAV-in-TAV configurations, to offer basic hemodynamic guidance for future interventions when currently implanted valves structurally degrade.MethodsSix TAV-in-TAV configurations were chosen: 23 mm Evolut-in-26 mm Evolut, 23 mm Evolut-in-23 mm SAPIEN 3, 26 mm Evolut-in-26 mm Evolut, 26 mm Evolut-in-23 mm SAPIEN 3, 23 mm SAPIEN3-in-26 mm Evolut, and 23 mm SAPIEN3-in-23 mm SAPIEN 3. Their hemodynamic performance was assessed in a pulse duplicator for 100 cycles. High-speed imaging and particle image velocimetry were performed to assess turbulence. Effective orifice area (EOA), pinwheeling index (PI), and Reynolds shear stress (RSS) were evaluated.ResultsThe largest mean EOA was obtained with 23 mm SAPIEN-in-26 mm Evolut (2.07 ± 0.06 cm2), and the smallest was obtained with 23 mm Evolut-in-23 mm SAPIEN (1.50 ± 0.04 cm2) (P < .001). The highest mean PI was obtained with SAPIEN-in-SAPIEN (26.5 ± 2.00%), and the lowest was obtained with 26 mm Evolut-in-26 mm Evolut (7.5 ± 1.6%) (P < .01). At peak systole, the least detrimental RSS range was obtained with 23 mm Evolut-in-26 mm Evolut (up to ∼340 Pa), and the most detrimental RSS range was obtained with 23 mm Evolut-in-SAPIEN (∼900 Pa) (P < .01).ConclusionsThis study shows that best hemodynamic parameters are TAV-specific (implanted and to be implanted). In addition, it shows that RSS levels, which are indicative of turbulence levels and associated with blood damage, are 2- to 3-fold higher after TAV-in-TAV.

Dataset Information

Differential expression of cartilage and bone-related proteins in pediatric and adult diseased aortic valves.

Publications

Differential expression of cartilage and bone-related proteins in pediatric and adult diseased aortic valves.

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