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Characteristics of TAV- and BAV-associated thoracic aortic aneurysms--smooth muscle cell biology, expression profiling, and histological analyses.

Abstract

OBJECTIVE
Past studies on the pathogenesis of thoracic aortic aneurysms have, by concentrating on histological and total tissue analyses, revealed several disease-relevant processes. Despite these studies, there is still a significant lack in the understanding of aneurysmal cell biology today. Hence, it was the goal of this study to assess differences between aneurysmal and healthy aortic smooth muscle cells (SMCs) on a broad - screening-like - basis, allowing us to formulate new hypotheses on the role of SMCs in thoracic aneurysm formation.
METHODS AND RESULTS
After histological characterization of a total of 16 samples from healthy aortas and thoracic aortic aneurysms (TAA) of patients with bicuspid (BAV) and tricuspid (TAV) aortic valves, we isolated aortic SMCs and subjected them to cell biological and gene expression analyses. The data obtained indicate that aneurysmal SMCs exert reduced proliferation and migration rates compared to controls. BAV TAA SMCs have significantly shorter telomeres, whereas TAV TAA SMCs showed a reduced metabolic activity. In BAV TAA SMCs osteopontin (OPN) expression was significantly elevated, and TAV TAA SMCs showed decreased expression of tissue inhibitor of metalloproteinase 3 (TIMP3).
CONCLUSION
Our study provides evidence that TAA-associated aortic wall disintegration in BAV and TAV TAAs shows similarities, but also significant differences. BAV and TAV TAAs differ with regard to medial elastic fiber mass and the occurrence of fibroblasts, SMC telomere length, metabolism, and gene expression. This study may form the basis for future in-depth analyses on the relevance of these findings in the pathophysiology of BAV and TAV TAAs.

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  • Publisher Full Text
  • Authors

    Blunder S, Messner B, Aschacher T, Zeller I, Türkcan A, Wiedemann D, Andreas M, Blüschke G, Laufer G, Schachner T, Bernhard D

    Source

    Atherosclerosis 220:2 2012 Feb pg 355-61

    MeSH

    Adult
    Aged
    Aorta, Thoracic
    Aortic Aneurysm, Thoracic
    Aortic Valve
    Austria
    Blotting, Western
    Case-Control Studies
    Cell Movement
    Cell Proliferation
    Cells, Cultured
    Elastic Tissue
    Fibroblasts
    Gene Expression Profiling
    Gene Expression Regulation
    Heart Defects, Congenital
    Humans
    Immunohistochemistry
    Middle Aged
    Muscle, Smooth, Vascular
    Myocytes, Smooth Muscle
    Osteopontin
    RNA, Messenger
    Real-Time Polymerase Chain Reaction
    Telomere Shortening
    Time Factors
    Tissue Inhibitor of Metalloproteinase-3

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22178424