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Entstehung und Progression der Aortenklappendegeneration

Auswirkungen von diabetischer Stoffwechsellage und Modulation der Extrazellulärmatrix
  • M. Barth
Stand der Wissenschaft
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Zusammenfassung

Kardiovaskuläre Erkrankungen sind eine der führenden Ursachen von steigenden Kosten im Gesundheitssystem westlicher Industrieländer. Die degenerative Aortenklappenerkrankung (DAE) stellt eine der Hauptdiagnosen dar und führt letztendlich zum Ersatz der betroffenen Klappe. Risikofaktoren für DAE sind Patientenalter, männliches Geschlecht und Rauchen. Auch Diabetes mellitus (DM) ist assoziiert mit dem höheren Risiko, an einer DAE zu erkranken. Prognostiziert wird eine Zunahme der Prävalenz von DM um 50 % bis 2030, weshalb DM in Zusammenhang mit kardiovaskulären Erkrankungen zunehmend bedeutender wird. Die Mechanismen und Zusammenhänge, die zur DAE führen, sind jedoch immer noch nicht völlig geklärt. Risikofaktoren und Pathophysiologie der DAE ähneln denen der Atherosklerose. Endothelschäden, Veränderungen des Bindegewebes, Lipideinlagerung, Entzündungsprozesse und letztlich Kalzifizierung finden sich in beiden Krankheitsbildern. Studien zeigen, dass bestimmte Proteoglykane (PG) in der Extrazellularmatrix (EZM) von degenerierten Klappen maßgeblich verändert und an den degenerativen Prozessen beteiligt sind. Weiterhin scheinen PG mit DM assoziiert zu sein; dies begründet die Hypothese, dass PG eine Schlüsselrolle zwischen DM und DAE spielen könnten. Das Ziel des vorgestellten Projekts ist es daher, das mechanistische Zusammenspiel von Aortenklappen- und Prothesendegeneration im Fokus von DM zu untersuchen. Dies könnte in Zukunft helfen, Ursachen für diese Erkrankung schneller zu erkennen oder präventiv zu handeln und das Prothesenmaterial für Klappenersatzeingriffe zu optimieren.

Schlüsselwörter

Diabetes Inflammation Kalzifikation, pathologische Proteoglykane Glykosaminoglykane 

Development and progression of aortic valve degeneration

Impacts of diabetic metabolic disorders and modulation of the extracellular matrix

Abstract

Cardiovascular diseases are the leading cause of increasing public health expenditure in western industrialized countries. Degenerative aortic valve diseases (DAVD) are among the most frequent diagnoses, ultimately resulting in aortic valve (AV) replacement. The prevalence of DAVD increases with age but male sex and smoking are also known risk factors. In addition, diabetes mellitus (DM) is also associated with an increased risk of DAVD. The prevalence of DM is estimated to double by 2030; therefore, DM will play an incremental role in the future concerning cardiovascular diseases. Nevertheless, the underlying mechanisms and circumstances leading to valvular degeneration are not yet fully understood. Several studies have highlighted that the risk factors and pathophysiology of DAVD show high similarity to those of atherosclerotic lesions. Processes, such as endothelial cell injury and adverse connective tissue remodeling, lipid accumulation, inflammation and finally calcification take place in both disease patterns. Recent studies investigating the role of proteoglycans (PG) implicated an essential involvement of these extracellular matrix components in degenerative processes of the AV. Moreover, studies have shown that PG are associated with diabetic disorders, which leads to the hypothesis that they may represent a mechanistic link between DM and AV degeneration. Thus, the aim of this project was to elucidate the mechanistic processes which lead to the degeneration of AV and valvular bioprosthetic materials in the course of DM. This might help to limit or even prevent DM-associated adverse events in the future and to optimize the design of bioprosthetic materials used for various AV replacement strategies.

Keywords

Diabetes Inflammation Calcification, pathologic Proteoglycans Glycosaminoglycans 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

M. Barth gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von der Autorin durchgeführten Studien an Menschen oder Tieren.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Universitätsklinikum DüsseldorfKlinik für Kardiovaskuläre Chirurgie, Forschungsgruppe Experimentelle ChirurgieDüsseldorfDeutschland

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