Suppressed MMP-9 Activity in Myocardial Infarction-Related Cardiogenic Shock Implies Diminished Rage Degradation.

Abstract

BACKGROUND:

Receptor for advanced glycation end products (RAGE) and its cleavage fragment soluble RAGE (sRAGE) are opposite players in inflammation. Enhanced monocytic RAGE expression and decreased plasma sRAGE levels are associated with higher mortality in infarction-related cardiogenic shock. Active matrix metalloproteinase-9 (MMP-9) has been implied in RAGE ectodomain cleavage and subsequently sRAGE shedding in vitro. We investigated MMP-9 activity in myocardial infarction-induced cardiogenic shock with regard to RAGE/sRAGE regulation.

METHODS AND RESULTS:

We determined MMP-9 serum activity by zymography and tissue inhibitor of matrix metalloproteinases (TIMP-1) expression by Western blot and correlated it to RAGE/sRAGE data in patients with cardiogenic shock after acute myocardial infarction (CS, n = 30), in patients with acute myocardial infarction without shock (AMI, n = 20) and in healthy volunteers (n = 20).MMP-9 activity is increased in AMI (P = 0.02 versus controls), but significantly decreased in CS with lowest levels in non-survivors (n = 13, P = 0.02 versus AMI). In all patients, MMP-9 activity correlated inversely with RAGE expression on circulating monocytes (r = -0.57; P = 0.0001; n = 50).TIMP-1 levels showed an inverse regulation in comparison to active MMP-9 with significantly decreased levels in AMI as compared with controls (P = 0.02 versus controls) and highest levels in non-survivors of CS (P <0.001 versus AMI).

CONCLUSIONS:

Serum MMP-9 activity is increased in acute myocardial infarction, but markedly suppressed in cardiogenic shock. Maintaining MMP-9 activity could be a therapeutic target to limit RAGE-induced deleterious inflammation in cardiogenic shock.

• Authors: Simina-Ramona Selejan, Lisa Hewera, Matthias Hohl, Andrey Kazakov, Sebastian Ewen, Ingrid Kindermann, Michael Böhm, Andreas Link
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 48 Issue 1 Pg. 18-28 (07 2017) ISSN: 1540-0514 [Electronic] United States
• PMID: 28608784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptor for Advanced Glycation End Products
• Tissue Inhibitor of Metalloproteinase-1
• Matrix Metalloproteinase 9

Topics

• Aged
• Aged, 80 and over
• Female
• Flow Cytometry
• Humans
• Leukocytes, Mononuclear (metabolism)
• Male
• Matrix Metalloproteinase 9 (blood, metabolism)
• Middle Aged
• Myocardial Infarction (blood, metabolism)
• Receptor for Advanced Glycation End Products (blood, metabolism)
• Shock, Cardiogenic (blood, metabolism)
• Tissue Inhibitor of Metalloproteinase-1 (blood, metabolism)