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.

Links

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

Institution

Cardiac Surgery Research Laboratory, Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna, Austria.

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