1. Academic Validation
  2. Effect of broad-spectrum matrix metalloproteinase inhibition on atherosclerotic plaque stability

Effect of broad-spectrum matrix metalloproteinase inhibition on atherosclerotic plaque stability

  • Cardiovasc Res. 2006 Aug 1;71(3):586-95. doi: 10.1016/j.cardiores.2006.05.009.
Jason L Johnson 1 Regina Fritsche-Danielson Margareta Behrendt Annika Westin-Eriksson Håkan Wennbo Margareta Herslof Marie Elebring Sarah J George William L McPheat Christopher L Jackson
Affiliations

Affiliation

  • 1 Bristol Heart Institute, University of Bristol, Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom.
Abstract

Objective: Matrix Metalloproteinases (MMPs) form a large family of enzymes that collectively can degrade all components of the extracellular matrix, and there is widespread interest in developing MMP inhibitors for the prevention of atherosclerotic plaque rupture. We have therefore investigated the effects of a broad-spectrum MMP Inhibitor, RS-130830, on plaque development and stability. This compound inhibits a wide range of MMPs at concentrations below 20 nmol/L.

Methods: Apolipoprotein E knockout mice were fed a Western diet. Dietary administration of RS-130830 commenced at the same time as fat-feeding and continued for 8, 12, 26 or 36 weeks. To investigate the effect of RS-130830 on established plaques, mice were fed high-fat diet for 16 weeks before initiation of drug treatment and were terminated 20 weeks after this.

Results: Broad-spectrum MMP inhibition was associated with a significant increase in plaque area, but there was no change in the incidence of plaque rupture. There were unfavourable changes in phenotypic characteristics associated with plaque instability, such as an increased lipid content and decreased collagen content.

Conclusions: These data suggest that broad-spectrum MMP inhibition RS-130830 does not have a beneficial effect on atherosclerosis in the apolipoprotein E knockout mouse model, and indicate that more selective compounds would be preferable.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-10398
    99.19%, MMP Inhibitor
    MMP