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Evidence for the Involvement of Matrix-Degrading Metalloproteinases (MMPs) in Atherosclerosis
Bethan A Brown1, Helen Williams1, Sarah J George1
1School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
Abstract:
Atherosclerosis leads to blockage of arteries, culminating in myocardial infarction, and stroke. The involvement of matrix-degrading metalloproteinases (MMPs) in atherosclerosis is established and many studies have highlighted the importance of various MMPs in this process. MMPs were first implicated in atherosclerosis due to their ability to degrade extracellular matrix components, which can lead to increased plaque instability. However, more recent work has highlighted a multitude of roles for MMPs in addition to breakdown of extracellular matrix proteins. MMPs are now known to be involved in various stages of plaque progression: from initial macrophage infiltration to plaque rupture. This chapter summarizes the development and progression of atherosclerotic plaques and the contribution of MMPs. We provide data from human studies showing the effect of MMP polymorphisms and the expression of MMPs in both the atherosclerotic plaque and within plasma. We also discuss work in animal models of atherosclerosis that show the effect of gain or loss of function of MMPs. Together, the data provided from these studies illustrate that MMPs are ideal targets as both biomarkers and potential drug therapies for atherosclerosis.
Insights
Matrix-degrading metalloproteinases (MMPs) play diverse roles in atherosclerosis, influencing plaque progression and instability. Targeting MMPs offers potential for novel biomarkers and therapies for cardiovascular diseases like heart attack and stroke.
Area of Science:
- Cardiovascular Biology
- Biochemistry
- Pathology
Background:
- Atherosclerosis involves arterial blockage, leading to myocardial infarction and stroke.
- Matrix-degrading metalloproteinases (MMPs) are implicated in atherosclerosis, initially for extracellular matrix degradation and plaque instability.
- Recent research reveals MMPs' broader roles in plaque progression, from macrophage infiltration to rupture.
Purpose of the Study:
- To summarize the role of MMPs in the development and progression of atherosclerotic plaques.
- To highlight MMPs as potential therapeutic targets and biomarkers for atherosclerosis.
Main Methods:
- Review of human studies on MMP polymorphisms and expression in plaques and plasma.
- Analysis of animal models demonstrating MMP gain and loss-of-function effects.
Main Results:
- MMPs contribute to various stages of atherosclerotic plaque development and progression.
- Human genetic data and animal models support MMP involvement in atherosclerosis.
Conclusions:
- MMPs are crucial in atherosclerotic plaque development and instability.
- MMPs represent promising targets for atherosclerosis biomarkers and drug therapies.