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 Aneurysmal Disease of the Abdominal Aorta

Histological changes

  • Extracellular matrix (collagen, elastin).
  • Cellular components – inflammatory infiltrates.

Genetics

Experimental models

  • Spontaneous animal models.
  • Pharmacologic models.
  • Dietary models.
  • Surgical models.

Causes of aneurysms

  • The role of proteases (elastases, collagenases, plasmin, matrix metalloproteinases) and proteases inhibitors ( α -1 antitrypsin, tissue inhibitor of metalloproteinases).
  • The role of inflammation.
  • The role of autoimmunity.
  • The role of atherosclerosis.
  • The role of hemodynamics.

V. Potential for intervention based on pathophysiology.

References

van Vlijmen-van Keulen CJ, Pals G, Rauwerda JA. Familial abdominal aortic aneurysm: a systematic review of a genetic background. Eur J Vasc Endovasc Surg 2002;24:105-116.

This article gives an overview of research data on the genetic background of AAA. Based on the familial clustering of the AAA, reported in 11-19% of AAA patients, a gene mutation in one of the structural proteins of the connective tissue is expected. However, no specific genetic factor responsible for familial AAA has been identified yet.

Carrell TW, Smith A, Burnand KG. Experimental techniques and models in the study of the development and treatment of abdominal aortic aneurysm. Br J Surg 1999;86:305-312.

This article discusses animal models and experimental techniques that have been described in the investigation of the pathophysiology of AAA and in the development of improved endovascular surgical and pharmacological therapies. The advantages of these models and some of the problems encountered in extrapolating experimental findings to the human condition are also discussed.

Rehm JP, Grange JJ, Baxter BT. The formation of aneurysms. Semin Vasc Surg 1998;11:193-202.

Recent progress in our understanding of the pathogenesis of aneurysmal disease is summarized in this article. The role of immunology, biochemistry, cell biology, and genetic issues is reviewed with special emphasis on the role of the local inflammatory infiltrates and the destructive proteolytic enzymes.

Grange JJ, Davis V, Baxter BT. Pathogenesis of abdominal aortic aneurysm: an update and look toward the future. Cardiovasc Surg 1997;5:256-265.

This article reviews current knowledge on the pathogenesis of abdominal aortic aneurysm. The role of atherosclerosis, inflammation, matrix changes and proteolysis is specifically addressed.

Thompson RW, Parks WC. Role of matrix metalloproteinases in abdominal aortic aneurysms. Ann N Y Acad Sci 1996;800:157-174.

The finding that elastolytic MMPs, particularly MMP-9 and MMP-2, are expressed and produced in increased amounts in human aneurysm tissue, has led to the possibility that these enzymes might serve as rational targets for pharmacotherapy in this disease. The role of matrix metalloproteinases in abdominal aortic aneurysm disease as well as the therapeutic implications of this role are outlined in this review.

Posted June 2010