Matrix metalloproteinase-9 (MMP-9) is a gelatinase that has been implicated in the pathogenesis of atherosclerosis and chronic obstructive pulmonary disease (COPD) in addition to 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 various 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 as well as 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.
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for both physiological and pathophysiological tissue remodeling. MMPs cleave all structural elements of the extracellular matrix, as well as process a variety of non-ECM substrates.
MMP-9 first termed 92-kDa type IV collagenase or gelatinase B, plays a major 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 important for embryo implantation, starting from the trophoblastic invasion during the early gestation period. MMP-9 is present in developing cardiac tissue and is expressed between 16 and 18 days of embryogenesis. MMP-9 is also reported to play a significant role in neovascularization through the proteolytic degradation of the proteins in the basal lamina of the blood vessels and a release of the biologically active form of vascular endothelial growth factor.
MMP-9 plays important role in immune cell function. In pathophysiological conditions, MMP-9 is upregulated during development and wound healing, as well as during pathologies that involve inflammatory processes, including arthritis, diabetes, and cancer. In these pathophysiological conditions, MMP-9 proteolytic properties contribute to stimulating the immune response to initiate pathogenesis and disease progression. MMP-9 robustly increases during several cardiovascular diseases, including hypertension, atherosclerosis, and myocardial infarction.
MMP-9 is secreted by a wide number of cell types, including neutrophils, macrophages, and fibroblasts.