Page 7 - GPD-3-1

Gene & Protein in Disease

EDITORIAL
The role of metalloproteinases in atherosclerosis

Raffaele Serra *
†
Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy

Metalloproteinases are multidomain zinc-dependent endopeptidases, also termed
metzincins, that are involved in extracellular matrix (ECM) turnover, proteolysis
of collagen, elastin and other ECM proteins, and several pathological pathways such
as chronic inflammation. Atherosclerosis is one of the most important causes of
1,2
cardiovascular disease and is strictly related to inflammatory processes and protease
activity. The occurrence of atherosclerotic plaque rupture may dictate, for example,
3,4
events such as myocardial infarction and stroke that are the primary contributors to
disability and mortality worldwide. Furthermore, plaque rupture is mainly caused by
5
the metalloproteinases that play a role in regulating the content of ECM proteins in the
fibrous cap and in the near regions of the necrotic core of plaques. MPs are also able to
3
influence all aspects of pathophysiology of atherosclerotic phenomena not only through
their proteolytic activity but also through their actions on endothelial cells, vascular
smooth muscle cells (VSMCs), and macrophages. 1-3
There are three main families of metalloproteinases, namely, matrix metalloproteinase
(MMP), which is the first identified and most widely known family; a disintegrin
and a metalloproteinase (ADAM); and a disintegrin and a metalloproteinase with
thrombospondin motif (ADAMTS). Metalloproteinases are physiologically inhibited
1,2
by tissue inhibitors of metalloproteinases (TIMPs) and help maintain ECM homeostasis. 1,2
Endothelial cells, VSMCs, and macrophages are cellular source of MMPs. In
† Associate Editor of Gene & Protein particular, overexpression of MMP-1, MMP-8, and MMP-13 has been found in unstable
in Disease plaques. Elevated MMP-2 plasma levels have been detected in coronary artery disease
*Corresponding author: (CAD) patients. Increased MMP-9 expression and activity is related to the recruitment of
Raffaele Serra several proinflammatory cytokines, both in coronary unstable plaques of CAD patients,
(rserra@unicz.it)
and in carotid unstable plaques of carotid artery stenosis (CAS) patients. MMP-9 is
Citation: Serra R. The role often used as a biomarker in several clinical scenarios in patients with atherosclerotic
of metalloproteinases in diseases. There is sufficient evidence from the current troves of research that targeting
1,2
atherosclerosis. Gene Protein Dis.
2024;3(1):2776. MMP could have therapeutic effects in patients with atherosclerotic diseases. 1,2
https://doi.org/10.36922/gpd.2776
ADAM members play an active role in the recruitment of inflammatory cells
Received: January 18, 2024 influencing atherosclerosis onset, progression, and complications, but, to date, there are
Published Online: March 18, 2024
no conclusive data on whether targeting these molecules may have therapeutic effects in
Copyright: © 2024 Author(s). patients with atherosclerosis. 1-3
This is an Open-Access article
distributed under the terms of the ADAMTS family is largely involved in atherosclerosis mainly for their ability to degrade
Creative Commons Attribution proteoglycans which compose early atherosclerotic lesions with intimal thickening,
License, permitting distribution,
and reproduction in any medium, and, in particular, ADAMTS-4 and ADAMTS-8 are also able to recruit monocyte/
provided the original work is macrophage population triggering chronic inflammation within the artery. Genome-
properly cited. wide association studies (GWASs) have found single-nucleotide polymorphisms within
Publisher’s Note: AccScience the genomic region of ADAMTS7, which are associated with CAD. Histologically, high
Publishing remains neutral with expression of ADAMTS-7 has been detected in plaques related to CAD and CAS. In fact,
regard to jurisdictional claims in
published maps and institutional ADAMTS-7 seems to play a key role in promoting VSMCs migration and neointima
affiliations. formation. 3

Volume 3 Issue 1 (2024) 1 https://doi.org/10.36922/gpd.2776