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(Circulation. 2001;103:2222.)
© 2001 American Heart Association, Inc.

Editorial

On Genetics, Inflammation, and Abdominal Aortic Aneurysm

Can Single Nucleotide Polymorphisms Predict the Outcome?

A. J. Marian, MD

From Baylor College of Medicine, Department of Medicine, Section of Cardiology, Houston, Tex.

Correspondence to A.J. Marian, MD, Associate Professor of Medicine, Section of Cardiology, One Baylor Plaza, 543E, Houston, TX 77030. E-mail amarian@bcm.tmc.edu

Key Words: Editorials • genetics • aneurysm • cytokines • polymorphism, single nucleotide

The late Professor Russell Ross proposed the "response to injury" hypothesis for the pathogenesis of atherosclerosis 25 years ago.^{1 2 3} This shifted the paradigm from the "fibrin incrustation" and "lipid transudation" hypotheses that were formulated in the mid-19th century by von Rokitansy and Virchow, respectively. Subsequent identification of growth and mitotic factors in the vessel wall that were responsible for the proliferation and migration of smooth muscle cells,¹ along with the landmark discovery of endothelium as a biologically active inner layer of vessels by Furchgott and colleagues,⁴ established the active role of blood vessels in pathological states. The findings of macrophages in the vessel wall and increased expression of proteins involved in inflammation suggested the active role of inflammation in the pathogenesis of a variety of vascular diseases, including abdominal aortic aneurysm (AAA).

AAA, a relatively common disease in the elderly, is a disease of the media that is characterized by degeneration of the extracellular matrix proteins. Degradation occurs as a consequence of complex interactions between genetic factors, inflammatory cytokines, matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), and others. The ensuing phenotype is dissolution and fragmentation of collagen and elastin, leading to expansion of the vessel wall that can no longer withstand the repetitive expansile force of systolic contraction.

Extracellular matrix proteins maintain the integrity of the vessel wall. Under normal circumstances, degradation of extracellular matrix proteins is minimal because MMPs are expressed at low levels and in inactive forms.⁵ The activation of MMPs requires the removal of an amino-terminal . . . [Full Text of this Article]

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