Vascular aneurysms: a perspective

Indian J Biochem Biophys. 2014 Dec;51(6):449-56.

Abstract

Aneurysms develop as a result of chronic inflammation of vascular bed, where progressive destruction of structural proteins, especially elastin and collagen of smooth muscle cells has been shown to manifest. The underlying mechanisms are an increase in local production of proinflammatory cytokines and subsequent increase in proteases, especially matrix metalloproteinases (MMPs) that degrade the structural proteins. The plasminogen system: urokinase-type PA (u-PA), tissue-type PA (t-PA) and plasminogen activator inhibitor-1 (PAI-1) and the MMPs system-MMPs and TIMPs contribute to the progression and development of aneurysms. Recent studies suggest that aneurysms may be genetically determined. To date, most observable candidate genes for aneurysm (elastin, collagen, fibrillin, MMPs and TIMPs) have been explored with little substantiation of the underlying cause and effect. Recently, overexpression of the MMP-2 gene has been suggested as an important phenomenon for aneurysm formation. Along with MMPs, matrix formation also depends on JNK (c-Jun N-terminal kinase) as its activation plays important role in downregulating several genes of matrix production. Under stress, activation of JNK by various stimuli, such as angiotensin II, tumor necrosis factor-α and interleukin-1β has been noted significantly in vascular smooth muscle cells. Several therapeutic indications corroborate that inhibition of MMP-2 and JNK is useful in preventing progression of vascular aneurysms. This review deals with the role of proteases in the progression of vascular aneurysm.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aneurysm / immunology*
  • Animals
  • Blood Vessels / immunology*
  • Cytokines / immunology*
  • Enzyme Activation
  • Humans
  • Models, Cardiovascular*
  • Models, Immunological*
  • Peptide Hydrolases / immunology*
  • Signal Transduction / immunology*

Substances

  • Cytokines
  • Peptide Hydrolases