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September 11, 2009Circulation ResearchOpen Access

A Role of Matrix Metalloproteinase-8 in Atherosclerosis

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Population

Atherosclerosis-prone apolipoprotein E-deficient mice; 2,000 patients with coronary artery disease; and 782…

Comparison

MMP8 gene inactivation and MMP8 gene variation vs MMP8+/+/apoE-/- controls and alternative alleles

Design

Preclinical

Follow-up

12 weeks (mice); 10 years (Bruneck study)

Discussion

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Overview

Supports MMP8 inhibition for atherosclerosis testing; leaves open translation to human event reduction.

Structured PICO

P
Population
Atherosclerosis-prone apolipoprotein E-deficient mice (6-week-old males fed Western diet for 12 weeks); 2,000 patients with coronary artery disease (>50% stenosis); and 782 subjects from the population-based prospective Bruneck Study.
I
Intervention
MMP8 gene inactivation (in mice) and MMP8 gene variation (SNP rs1940475) (in humans)
C
Comparator
MMP8+/+/apoE-/- controls (in mice) and alternative alleles (in humans)
O
Outcome
Extent of atherosclerotic lesions (mice) and extent/progression of atherosclerosis (humans)surrogate

MMP8 plays a causal role in atherogenesis, and its genetic variation is associated with the extent and progression of atherosclerosis in humans.

Limitations

  • Only assessed atherosclerosis in the aorta following a Western diet for 12 weeks
  • No Ang II level data available for CAD patients and Bruneck cohort

Cite This Study

A 2009 study studied this question.

synapsesocial.com/papers/6a8a3ca6451a22fc7efb9468https://doi.org/10.1161/circresaha.109.200279
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Serum Matrix Metalloproteinase-8 Concentrations Are Associated With Cardiovascular Outcome in Men2007 · 182 citations
  2. 2Macrophage Metalloelastase Accelerates the Progression of Atherosclerosis in Transgenic Rabbits2006 · 155 citations
  3. 3Matrix Metalloproteinase-2 and −9 Differentially Regulate Smooth Muscle Cell Migration and Cell-Mediated Collagen Organization2003 · 315 citations
  4. 4Cardiac remodelling in end stage heart failure: upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP2002 · 140 citations
  5. 5Vascular Inflammation and the Renin-Angiotensin System2002 · 584 citations