TY - JOUR
T1 - Matrix metalloproteinase-9
T2 - Many shades of function in cardiovascular disease
AU - Yabluchanskiy, Andriy
AU - Ma, Yonggang
AU - Iyer, Rugmani Padmanabhan
AU - Hall, Michael E.
AU - Lindsey, Merry L.
PY - 2013/11/1
Y1 - 2013/11/1
N2 - 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.
AB - 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.
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U2 - 10.1152/physiol.00029.2013
DO - 10.1152/physiol.00029.2013
M3 - Review article
C2 - 24186934
AN - SCOPUS:84887108043
VL - 28
SP - 391
EP - 403
JO - Physiology
JF - Physiology
SN - 1548-9213
IS - 6
ER -