Do metalloproteinases destabilize vulnerable atherosclerotic plaques?

Area of Science:

• Cardiovascular Biology
• Enzymology
• Atherosclerosis Research

Background:

• Atherosclerotic plaque rupture and thrombosis are primary causes of myocardial infarction.
• Matrix metalloproteinases (MMPs) are enzymes that remodel the extracellular matrix, influencing plaque stability.
• MMPs may stabilize plaques by promoting smooth muscle cell functions or destabilize them through matrix degradation and inflammation.

Purpose of the Study:

• To review evidence on the dual role of matrix metalloproteinases in atherosclerotic plaque stabilization and rupture.
• To elucidate the mechanisms by which MMPs influence plaque vulnerability.
• To assess the therapeutic potential of targeting MMPs in coronary artery disease.

Main Methods:

• Review of genetically modified mouse models (knockouts and overexpression).
• Analysis of human biomarker and genetic studies.
• Examination of evidence from mouse and rabbit studies on MMP activity and plaque stability.

Main Results:

• Inhibition of MMPs in mice generally increases plaque stability.
• Genetic studies show mixed effects of individual MMPs, indicating both protective and harmful roles.
• Overexpression of MMP-9 and MMP-12 in animal models decreases plaque stability.
• Human studies link increased MMP activity to vascular repair and myocardial infarction.

Conclusions:

• Matrix metalloproteinases have a complex, dual role in plaque stabilization and rupture, dependent on disease stage, site, and severity.
• Dysregulated MMP activity in end-stage coronary artery disease is a promising therapeutic target.