Matrix metalloproteinase-9: Many shades of function in cardiovascular disease

Physiology (Bethesda). 2013 Nov;28(6):391-403. doi: 10.1152/physiol.00029.2013.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / enzymology*
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular System / enzymology*
  • Cardiovascular System / pathology
  • Cardiovascular System / physiopathology
  • Fibrosis
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Inflammation / enzymology
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Matrix Metalloproteinase 9 / chemistry
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Protein Conformation
  • Signal Transduction
  • Structure-Activity Relationship
  • Substrate Specificity


  • MMP9 protein, human
  • Matrix Metalloproteinase 9