Matrix Metalloproteinases in Cardiovascular Disease Mechanisms

Matrix metalloproteinases (MMPs) form a family of zinc-dependent proteolytic enzymes that remodel the extracellular matrix of the vascular wall and regulate a range of cellular processes. In the context of cardiovascular disease, imbalances in MMP activity drive pathological changes in atherosclerotic plaque formation, progression and rupture, as well as adverse myocardial remodelling following infarction. Upregulation of collagenases and gelatinases such as MMP-1, MMP-2, MMP-9 and MMP-12 in response to inflammatory stimuli promotes extracellular matrix degradation, thinning of the fibrous cap and infiltration by macrophages, increasing the risk of plaque instability and thrombotic events. Conversely, tissue inhibitors of metalloproteinases (TIMPs) provide a counter-regulatory mechanism that when overwhelmed or downregulated permits unchecked proteolysis. MMPs also modulate cellular signalling pathways that influence vascular smooth muscle cell migration, endothelial function and neovascularisation within lesions. Understanding the spatio-temporal regulation of MMPs has underscored their global significance as biomarkers of disease severity and as potential therapeutic targets, informing both pharmacological and interventional strategies to stabilise plaques and limit post-ischaemic remodelling.

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Matrix Metalloproteinases in Cardiovascular Disease Mechanisms publication trend

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Technical terms

Matrix metalloproteinases (MMPs): Zinc-dependent endopeptidases that degrade extracellular matrix components and modulate cellular signalling.

Extracellular matrix (ECM): A network of proteins and polysaccharides providing structural support to tissues and regulating cell behaviour.

Atherosclerotic plaque: A lesion in the arterial wall composed of lipids, inflammatory cells, connective tissue and fibrous cap that can impede blood flow or rupture.

Plaque instability: The propensity of an atherosclerotic lesion to undergo fibrous cap thinning and rupture, precipitating thrombotic events.

Tissue inhibitors of metalloproteinases (TIMPs): Endogenous proteins that bind to and inhibit MMP activity, maintaining proteolytic balance.

References

1. Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice. Cardiovascular Diabetology (2023).
2. Matrix metalloproteinases in coronary artery disease and myocardial infarction. Basic Research in Cardiology (2023).
3. Matrix metallopeptidase 9 contributes to the beginning of plaque and is a potential biomarker for the early identification of atherosclerosis in asymptomatic patients with diabetes. Frontiers in Endocrinology (2024).