Low matrix metalloproteinase levels precede vascular lesion formation in the JCR: LA-cp rat

David Wilson, Hamid Massaeli, James C. Russell, Grant N. Pierce, Peter Zahradka

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Clinically significant occlusive vascular lesions contain more extracellular matrix (ECM) proteins and lipid deposition than healthy vascular tissue. The events leading to this condition remain unresolved. One possibility is that ECM deposition may exceed ECM degradation which would contribute to the expansion of the vascular lesion. Utilizing lean (+/?) and insulin-resistant, corpulent (cp/cp) JCR:LA-cp rats, which are predisposed to develop vascular lesions, we have compared the matrix metalloproteinase (MMP) profile prior to the development of significant vascular lesions. Analysis of serum MMPs revealed that cp/cp rats have lower circulating levels than (+/?) controls. This is observed prior to the development of any noticeable atherosclerotic lesions. It also occurs as the hyperinsulinemia and insulin resistance is first developing in these rats. Female corpulent animals, which are less prone to develop vascular lesions, also exhibit a depressed serum MMP profile of a similar magnitude to their male counterparts. Primary vascular smooth muscle cells isolated from cp/cp animals also showed a reduction in secreted MMP compared with cells derived from +/? lean controls. We conclude that reduced MMP levels could lead to increased ECM accumulation and thus contribute to early vascular lesion formation.

Original languageEnglish
Pages (from-to)151-155
Number of pages5
JournalMolecular and Cellular Biochemistry
Volume249
Issue number1-2
DOIs
Publication statusPublished - 1 Jul 2003
Externally publishedYes

    Fingerprint

Keywords

  • Corpulent gene
  • JCR:LA-cp rat
  • Matrix metalloproteinase
  • Smooth muscle

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this