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Detection of the terminal complement complex in patient plasma following acute myocardial infarction
1Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612.
Insights
Inflammation after acute myocardial infarction (AMI) involves the complement system. Complement activation products, including the terminal complement complex (TCC), significantly increase, suggesting a role in myocardial tissue damage.
Area of Science:
- Immunology
- Cardiology
- Pathophysiology
Background:
- Mechanisms of inflammation driving myocardial damage post-acute myocardial infarction (AMI) remain unclear.
- Depressed complement component levels post-MI suggest complement system involvement in vascular injury.
- The complement (C) system's role in myocardial inflammation requires further elucidation.
Purpose of the Study:
- To assess the complement system's role as a mediator of myocardial inflammation following AMI.
- To quantify specific complement activation products in patients post-AMI.
- To investigate complement activation in relation to myocardial tissue damage.
Main Methods:
- Quantified plasma levels of terminal complement complex (TCC), C1rC1s-C1 inhibitor complex, C3bBbP complex, C3a des-Arg, and C5a des-Arg in 41 AMI patients.
- Measured complement activation products at 16 hours post-AMI and during reinfarction events.
- Compared levels to non-inflammatory myocardial conditions.
Main Results:
- Plasma TCC and C1rC1s-C1 inhibitor complex concentrations increased significantly (up to 32-fold and 8-fold, respectively) 16 hours post-AMI (P < 0.001).
- C3bBbP complex, C3a des-Arg, and C5a des-Arg increased over 2-fold post-AMI (P < 0.001), with minimal detection in non-inflammatory states.
- TCC concentrations increased over 150% (P < 0.001) in patients who reinfarcted after initial hospitalization.
Conclusions:
- Complement activation is demonstrably increased following acute myocardial infarction.
- Inflammatory mediators of the complement system likely contribute to myocardial tissue damage during AMI.
- Further research into complement inhibition may offer therapeutic strategies for AMI recovery.
Abstract:
The mechanisms of inflammation responsible for the myocardial tissue damage seen after an acute myocardial infarction (AMI) have not been clearly identified. Recent lines of evidence, demonstrating depressed sera levels of individual complement components in patients after myocardial infarction, have suggested involvement of the complement (C) system in micro- and macrovascular injury subsequent to AMI. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation including, the terminal complement complex (TCC) the cytolytic component of the complement system, C1rC1s-C1 inhibitor complex and C3bBbP complex, formed following activation of the classical and alternative pathway, respectively, and anaphylatoxins C3a and C5a in 41 patients following AMI. Plasma TCC and C1rC1s-C1 inhibitor complex concentrations increased up to 32-fold (P less than 0.001) and 8-fold (P less than 0.001), respectively, while the C3bBbP complex, C3a des-Arg and C5a des-Arg each increased over 2-fold (P less than 0.001) 16 h after AMI, and were only minimally detectable during non-inflammatory myocardial conditions. Furthermore, TCC concentrations increased over 150% (P less than 0.001) one day after patients reinfarcted, subsequent to hospitalization for a primary AMI. These results demonstrate activation of complement after AMI and suggest that inflammatory mediators of the complement system may contribute to myocardial tissue damage during the infarction process.