Smooth muscle phenotypic modulation is an early event in aortic aneurysms

Gorav Ailawadi, Christopher W. Moehle, Hong Pei, Sandra P. Walton, Zequan Yang, Irving L. Kron, Christine L. Lau, Gary K. Owens

Research output: Contribution to journalArticle

148 Scopus citations

Abstract

Objectives: Vascular smooth muscle cells can undergo profound changes in phenotype, defined by coordinated repression of smooth muscle cell marker genes and production of matrix metalloproteinases in response to injury. However, little is known of the role of smooth muscle cells in aortic aneurysms. We hypothesized that smooth muscle cells undergo phenotypic modulation early in the development of aortic aneurysms. Methods: Abdominal aortas from C57B6 mice (n = 79) were perfused with elastase or saline (control) and harvested at 1, 3, 7, or 14 days. Aortas were analyzed by means of quantitative polymerase chain reaction and immunohistochemistry for smooth muscle cell marker genes, including SM22A, smooth muscle α-actin, and matrix metalloproteinases 2 and 9. In complimentary experiments human aneurysms (n = 10) and control aorta (n = 10) were harvested at the time of surgical intervention and analyzed. Results: By 14 days, aortic diameter was larger after elastase perfusion compared with control diameter (100% ± 9.6% vs 59.5% ± 18.9%, P = .0002). At 7 days, elastase-perfused mice had a 78% and 85% reduction in SM22α and smooth muscle α-actin expression, respectively, compared with that seen in control animals well before aneurysms were present, and these values remained repressed at 14 days. Immunohistochemistry confirmed less SM22α and smooth muscle α-actin in experimental aneurysms at 14 days in concert with increased matrix metalloproteinase 2 and 9 expression at 7 and 14 days. Similarly, human aneurysms had less SM22α and smooth muscle α-actin and increased matrix metalloproteinase 2 and 9 staining, compared with control values, as determined by means of quantitative polymerase chain reaction. Conclusions: Aneurysms demonstrate smooth muscle cell phenotypic modulation characterized by downregulation of smooth muscle cell marker genes and upregulation of matrix metalloproteinases. These events in experimental models occur before aneurysm formation. Targeting smooth muscle cells to a reparative phenotype might provide a novel therapy in the treatment of aortic aneurysms.

Original languageEnglish (US)
Pages (from-to)1392-1399
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume138
Issue number6
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Smooth muscle phenotypic modulation is an early event in aortic aneurysms'. Together they form a unique fingerprint.

  • Cite this

    Ailawadi, G., Moehle, C. W., Pei, H., Walton, S. P., Yang, Z., Kron, I. L., Lau, C. L., & Owens, G. K. (2009). Smooth muscle phenotypic modulation is an early event in aortic aneurysms. Journal of Thoracic and Cardiovascular Surgery, 138(6), 1392-1399. https://doi.org/10.1016/j.jtcvs.2009.07.075