Abdominal aortic aneurysm as a complex multifactorial disease: Interactions of polymorphisms of inflammatory genes, features of autoimmunity, and current status of MMPs

William H. Pearce*, Vera P. Shively

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contribution

87 Scopus citations

Abstract

The role of matrix metalloproteinases (MMPs) in the pathogenesis of abdominal aortic aneurysm (AAA) has focused on the degradation of the extracellular matrix (ECM). The new frontier of MMP biology involves the role of MMPs in releasing cryptic fragments and neoepitopes from the ECM and the impact of MMPs on the regulation of the inflammatory response. The ECM is a complex structure, much more important than an inert scaffold. Both MMP-2 and MMP-9 expose a cryptic epitope that controls angiogenesis. MMPs inhibit angiogenesis through the release of endostatin, endorepellin, arresten, canstatin, and tumstatin. Other breakdown products of the ECM include fragments of fragmin and elastin degradation products (EDPs). In addition, the ECM contains embedded vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β). Inflammation is a complex, highly regulated system that involves the identification of injury or infection, response to the injury or infection, repair and healing, and return to normal homeostasis. In some instances, the inflammatory process leads to a pathologic process that is damaging to the host. MMPs play an important role in the control of the inflammatory response through the modification of proinflammatory cytokines, chemokines, and shedding of membrane receptors. Genetic association studies have been performed to help determine the genetic risk associated with certain single nucleotide polymorphisms (SNPs) However, because of the variability in the patient populations and the size of the population, it is difficult to draw any conclusions from these studies. While the etiology of AAA remains unknown, understanding of the inflammatory process and its regulatory points will develop new strategies for the treatment of AAA. Perhaps one difficulty with understanding the pathogenesis of AAA is the lack of precise definition of the phenotype.

Original languageEnglish (US)
Title of host publicationThe Abdominal Aortic Aneurysm
Subtitle of host publicationGenetics, Pathophysiology, and Molecular Biology
PublisherBlackwell Publishing Inc.
Pages117-132
Number of pages16
ISBN (Print)1573316571, 9781573316576
DOIs
StatePublished - Nov 2006

Publication series

NameAnnals of the New York Academy of Sciences
Volume1085
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Aneurysm
  • Inflammation
  • MMPs
  • Metalloproteinases
  • Polymorphisms

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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