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Degenerative valve disease and bioprostheses: risk assessment, predictive diagnosis, personalised treatments.

ABSTRACT: Aortic stenosis (AS) is the most frequent valvular heart disease. Severe AS results in concentric left ventricular hypertrophy, and ultimately, the heart dilates and fails. During a long period of time patients remain asymptomatic. In this period a pathology progression should be monitored and effectively thwarted by targeted measures. A cascade of cellular and molecular events leads to chronic degeneration of aortic valves. There are some molecular attributes characteristic for the process of valvular degeneration with clear functional link between shifted cell-cycle control, calcification and tissue remodelling of aortic valves. Bioactivity of implanted bioprosthesis is assumed to result in its dysfunction. Age, gender (females), smoking, Diabetes mellitus, and high cholesterol level dramatically shorten the re-operation time. Therefore, predictive and preventive measures would be highly beneficial, in particular for young female diabetes-predisposed patients. Molecular signature of valvular degeneration is reviewed here with emphases on clinical meaning, risk-assessment, predictive diagnosis, individualised treatments.

SUBMITTER: Yeghiazaryan K

PROVIDER: S-EPMC3405368 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Degenerative valve disease and bioprostheses: risk assessment, predictive diagnosis, personalised treatments.

Yeghiazaryan Kristina K Skowasch Dirk D Bauriedel Gerhard G Schild Hans H HH Golubnitschaja Olga O

The EPMA journal 20110301 1

Aortic stenosis (AS) is the most frequent valvular heart disease. Severe AS results in concentric left ventricular hypertrophy, and ultimately, the heart dilates and fails. During a long period of time patients remain asymptomatic. In this period a pathology progression should be monitored and effectively thwarted by targeted measures. A cascade of cellular and molecular events leads to chronic degeneration of aortic valves. There are some molecular attributes characteristic for the process of v ...[more]

PMID: 23199131

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Project description:This review describes the first studies on successful conversion of porcine soft-tissue bioprostheses into viable permanently functional tissue in humans. This process includes gradual degradation of the porcine tissue, with concomitant neo-vascularization and reconstruction of the implanted bioprosthesis with human cells and extracellular matrix. Such a reconstruction process is referred to in this review as "humanization". Humanization was achieved with porcine bone-patellar-tendon-bone (BTB), replacing torn anterior-cruciate-ligament (ACL) in patients. In addition to its possible use in orthopedic surgery, it is suggested that this humanization method should be studied as a possible mechanism for converting implanted porcine bioprosthetic heart-valves (BHV) into viable tissue valves in young patients. Presently, these patients are only implanted with mechanical heart-valves, which require constant anticoagulation therapy. The processing of porcine bioprostheses, which enables humanization, includes elimination of ?-gal epitopes and partial (incomplete) crosslinking with glutaraldehyde. Studies on implantation of porcine BTB bioprostheses indicated that enzymatic elimination of ?-gal epitopes prevents subsequent accelerated destruction of implanted tissues by the natural anti-Gal antibody, whereas the partial crosslinking by glutaraldehyde molecules results in their function as "speed bumps" that slow the infiltration of macrophages. Anti-non gal antibodies produced against porcine antigens in implanted bioprostheses recruit macrophages, which infiltrate at a pace that enables slow degradation of the porcine tissue, neo-vascularization, and infiltration of fibroblasts. These fibroblasts align with the porcine collagen-fibers scaffold, secrete their collagen-fibers and other extracellular-matrix (ECM) components, and gradually replace porcine tissues degraded by macrophages with autologous functional viable tissue. Porcine BTB implanted in patients completes humanization into autologous ACL within ~2 years. The similarities in cells and ECM comprising heart-valves and tendons, raises the possibility that porcine BHV undergoing a similar processing, may also undergo humanization, resulting in formation of an autologous, viable, permanently functional, non-calcifying heart-valves.

Dataset Information

Degenerative valve disease and bioprostheses: risk assessment, predictive diagnosis, personalised treatments.

Publications

Degenerative valve disease and bioprostheses: risk assessment, predictive diagnosis, personalised treatments.

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