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	Andriy Yabluchanskiy, Yonggang Ma, Rugmani Padmanabhan Iyer, Michael E Hall, Merry L Lindsey
Journal	Physiology (Bethesda, Md.) (Physiology (Bethesda)) Vol. 28 Issue 6 Pg. 391-403 (Nov 2013) ISSN: 1548-9221 [Electronic] United States
PMID	24186934 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review)
Chemical References	MMP9 protein, human Matrix Metalloproteinase 9
Topics	Animals Cardiovascular Diseases (enzymology, genetics, pathology, physiopathology) Cardiovascular System (enzymology, pathology, physiopathology) Fibrosis Gene Expression Regulation, Enzymologic Humans Inflammation (enzymology, pathology, physiopathology) Matrix Metalloproteinase 9 (chemistry, genetics, metabolism) Protein Conformation Signal Transduction Structure-Activity Relationship Substrate Specificity

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