title: Matrix metalloproteinase-9: Many shades of function in cardiovascular disease.
abstract: Matrix metalloproteinase (MMP)-9, one of the most widely investigated MMPs, regulates pathological remodeling processes that involve inflammation and fibrosis in cardiovascular disease. MMP-9 directly degrades extracellular matrix (ECM) proteins and activates cytokines and chemokines to regulate tissue remodeling. MMP-9 deletion or inhibition has proven overall beneficial in multiple animal models of cardiovascular disease. As such, MMP-9 expression and activity is a common end point measured. MMP-9 cell-specific overexpression, however, has also proven beneficial and highlights the fact that little information is available on the underlying mechanisms of MMP-9 function. In this review, we summarize our current understanding of MMP-9 physiology, including structure, regulation, activation, and downstream effects of increased MMP-9. We discuss MMP-9 roles during inflammation and fibrosis in cardiovascular disease. By concentrating on the substrates of MMP-9 and their roles in cardiovascular disease, we explore the overall function and discuss future directions on the translational potential of MMP-9 based therapies.
authors.affiliation: 1San Antonio Cardiovascular Proteomics Center, San Antonio, Texas;
authors.forename: Andriy
authors.initials: A
authors.lastname: Yabluchanskiy
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Ma
authors.forename: Rugmani Padmanabhan
authors.initials: RP
authors.lastname: Iyer
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hall
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002319:Cardiovascular System / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D005355:Fibrosis; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9