TY - JOUR
T1 - Matrix metalloproteinase (MMP)-9
T2 - A proximal biomarker for cardiac remodeling and a distal biomarker for inflammation
AU - Halade, Ganesh V.
AU - Jin, Yu Fang
AU - Lindsey, Merry L.
N1 - Funding Information:
We acknowledge support from NIH-NCCAM K99AT006704 to GVH; from NSF 0649172 , NIH EB009496 , and NIH 1SC2 HL101430 to Y-FJ and from NHLBI HHSN 268201000036C (N01-HV-00244) for the UTHSCSA Cardiovascular Proteomics Center and R01 HL-075360, the Max and Minnie Tomerlin Voelcker Fund , and the Veteran's Administration (Merit) to MLL.
Funding Information:
ML Lindsey and GV Halade have current grant funding from Amylin Pharmaceuticals. This article is unrelated to that project.
PY - 2013/7
Y1 - 2013/7
N2 - Adverse cardiac remodeling following myocardial infarction (MI) remains a significant cause of congestive heart failure. Additional and novel strategies that improve our ability to predict, diagnose, or treat remodeling are needed. Numerous groups have explored single and multiple biomarker strategies to identify diagnostic prognosticators of remodeling progression, which will improve our ability to promptly and accurately identify high-risk individuals. The identification of better clinical indicators should further lead to more effective prediction and timely treatment. Matrix metalloproteinase (MMP-9) is one potential biomarker for cardiac remodeling, as demonstrated by both animal models and clinical studies. In animal MI models, MMP-9 expression significantly increases and is linked with inflammation, diabetic microvascular complications, extracellular matrix degradation and synthesis, and cardiac dysfunction. Clinical studies have also established a relationship between MMP-9 and post-MI remodeling and mortality, making MMP-9 a viable candidate to add to the multiple biomarker list. By definition, a proximal biomarker shows a close relationship with its target disease, whereas a distal biomarker exhibits non-targeted disease modifying outcomes. In this review, we explore the ability of MMP-9 to serve as a proximal biomarker for cardiac remodeling and a distal biomarker for inflammation. We summarize the current molecular basis and clinical platform that allow us to include MMP-9 as a biomarker in both categories.
AB - Adverse cardiac remodeling following myocardial infarction (MI) remains a significant cause of congestive heart failure. Additional and novel strategies that improve our ability to predict, diagnose, or treat remodeling are needed. Numerous groups have explored single and multiple biomarker strategies to identify diagnostic prognosticators of remodeling progression, which will improve our ability to promptly and accurately identify high-risk individuals. The identification of better clinical indicators should further lead to more effective prediction and timely treatment. Matrix metalloproteinase (MMP-9) is one potential biomarker for cardiac remodeling, as demonstrated by both animal models and clinical studies. In animal MI models, MMP-9 expression significantly increases and is linked with inflammation, diabetic microvascular complications, extracellular matrix degradation and synthesis, and cardiac dysfunction. Clinical studies have also established a relationship between MMP-9 and post-MI remodeling and mortality, making MMP-9 a viable candidate to add to the multiple biomarker list. By definition, a proximal biomarker shows a close relationship with its target disease, whereas a distal biomarker exhibits non-targeted disease modifying outcomes. In this review, we explore the ability of MMP-9 to serve as a proximal biomarker for cardiac remodeling and a distal biomarker for inflammation. We summarize the current molecular basis and clinical platform that allow us to include MMP-9 as a biomarker in both categories.
KW - Biomarker
KW - Cardiovascular
KW - Congestive heart failure
KW - Inflammation
KW - MMP-9
KW - Myocardial infarction
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U2 - 10.1016/j.pharmthera.2013.03.009
DO - 10.1016/j.pharmthera.2013.03.009
M3 - Review article
C2 - 23562601
AN - SCOPUS:84877924467
VL - 139
SP - 32
EP - 40
JO - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
JF - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
SN - 0163-7258
IS - 1
ER -