Matrix metalloproteinase-9 (MMP-9) is a gelatinase implicated in the pathogenesis of atherosclerosis, chronic obstructive pulmonary disease (COPD), and tumor formation and metastasis. Accordingly, several studies have associated elevated serum levels of MMP-9 with many chronic inflammatory conditions, including coronary artery disease, COPD, arthritis, and metabolic syndrome. Notably, high levels of MMP-9 have been associated with plaque progression, instability, and rupture. These effects exaggerate the inflammatory process, promoting atherosclerosis and increasing the risk of atherothrombosis and cardiovascular events.
Thus, MMP-9 has emerged as a novel disease marker and a therapeutic target. MMP-9, like other MMPs, belongs to a superfamily of zinc-containing proteases and has been shown to associate with tumorigenesis. Overexpression of tissue MMPs has been correlated with progression in many tumor types, and overexpression of MMP-9 has been found in colorectal adenomas and carcinomas. A significant positive correlation has also been found between tissue MMP-9 and the stage of colorectal tumors at diagnosis. Elevated expression of MMP-9, along with MMP-2, is usually seen in invasive and highly tumorigenic cancers such as colorectal tumors, gastric carcinoma, pancreatic carcinoma, breast cancer, oral cancer, melanoma, malignant gliomas, chondrosarcoma, gastrointestinal adenocarcinoma. Levels are also increased in malignant astrocytoma, carcinomatous meningitis, and brain metastases.
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Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for physiological and pathophysiological tissue remodeling. They cleave all structural elements of the extracellular matrix and process a variety of non-ECM substrates.
MMP-9, first termed 92-kDa type IV collagenase or gelatinase B, plays a significant role in the degradation of ECM in a large spectrum of physiology and pathophysiology processes that involve tissue remodeling. For example, MMP-9 expression is essential for embryo implantation, starting from the trophoblastic invasion during early gestation. MMP-9 is present in developing cardiac tissue and is expressed between 16 and 18 days of embryogenesis. MMP-9 has also been reported to play a significant role in neovascularization through the proteolytic degradation of proteins in the basal lamina of blood vessels and the release of biologically active forms of vascular endothelial growth factors.
MMP-9 plays a vital role in immune cell function. In pathophysiological conditions, MMP-9 is upregulated during development and wound healing and during pathologies involving inflammatory processes, including arthritis, diabetes, and cancer. MMP-9 proteolytic properties stimulate the immune response to initiate pathogenesis and disease progression in these pathophysiological conditions. MMP-9 robustly increases during several cardiovascular diseases, including hypertension, atherosclerosis, and myocardial infarction.
Many cell types, including neutrophils, macrophages, and fibroblasts, secrete MMP-9.
Important Note
The measurement of Matrix metalloproteinase-9 (MMP-9) is only performed for research purposes in clinical studies and experimental protocols.
