CD59 prevents human complement-mediated injuries in isolated guinea pig hearts
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Published on: March 18, 2019
Suhua Wu1, Hong Ma, Shoujian Huang
1Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University of Medical Sciences (SUMS), Guangzhou 510080, China. wusuhua@163.net
Insights
Activated human complement proteins directly cause myocardial injury in guinea pig hearts. The complement inhibitor CD59 significantly protects against this complement-mediated cardiac damage, highlighting its potential therapeutic role.
Area of Science:
- Cardiovascular Research
- Immunology
- Complement System Biology
Background:
- The complement system, a crucial part of innate immunity, can paradoxically mediate tissue damage.
- Complement-mediated injury is implicated in various cardiovascular pathologies.
- Understanding the direct effects of complement activation on the heart is essential for developing targeted therapies.
Purpose of the Study:
- To investigate complement-mediated myocardial injury in an isolated guinea pig working heart model.
- To evaluate the cardioprotective efficacy of CD59 against complement-induced cardiac damage.
Main Methods:
- Isolated guinea pig working hearts were perfused with plasma and zymosan to induce complement activation.
- Experimental groups included inactivated plasma (control), normal plasma, and normal plasma with CD59.
- Cardiac function (e.g., cardiac output, developed pressure) and electrocardiograms were monitored.
- Immunohistochemistry was used to detect complement components (C3a, C5b-9) in myocardial tissue.
Main Results:
- Perfusion with normal plasma and zymosan induced significant cardiac dysfunction, including decreased cardiac output and developed pressure, and ECG abnormalities.
- Immunohistochemistry confirmed the deposition of C3a and C5b-9 in the myocardium of hearts exposed to normal plasma.
- Hearts treated with CD59 exhibited preserved cardiac function and minimal complement deposition, similar to controls.
Conclusions:
- Human complement activation directly injures isolated guinea pig working hearts.
- CD59 effectively inhibits complement-mediated myocardial damage, demonstrating significant cardioprotective effects.
- These findings support the potential of CD59 as a therapeutic agent to mitigate complement-induced cardiac injury.
Objective:
To assess complement-mediated myocardial injury on isolated guinea pig working hearts and cardioprotective effects of CD59.
Methods:
Using a modified Langendorff apparatus, isolated guinea-pig working hearts were perfused with a modified Krebs Henseleit buffer containing 3% heat-inactivated human plasma and zymosan (IPZ) (control) (n = 10), 3% normal human plasma and zymosan (NPZ) (n = 10), or 3% normal human plasma and zymosan and 1.5 microg/ml CD59 (NPZC) (n = 10), respectively. Epicardial electrocardiogram (ECG), cardiac output (CO), coronary arterial flow (CF), maximum left ventricular developed pressure (LVP(max)), maximum left ventricular developed pressure increase rate (+ dp/dt(max)), maximum left ventricular developed pressure decrease rate (- dp/dt(max)) and heart rate (HR) were recorded at 0, 15, 30, 45 and 60 min of treatment. After the experiment, immunohistochemical examination was performed to detect the presence of C3a or C5b-9 in the myocardium of the isolated hearts.
Results:
Compared the IPZ group, hearts treated with NPZ showed a slight depression on ST segments of epicardial ECG at 15 min, a significant elevation between 30 min to 60 min, a decrease in CF, CO, LVP(max), + dp/dt(max) and - dp/dt(max), and an increase in HR at 15 min. The observed alterations in CF, CO, LVP(max), + dp/dt(max) and - dp/dt(max) remained decreased, while the HR remained increased until the end of the protocol. The all above parameters of hearts treated with NPZC were similar to the control group (IPZ) at any given time. Immunohistochemical examination showed positive signals of C3a and C5b-9 in the myocardium of hearts treated with NPZ. C3a was positive in NPZC, and C3a and C5b-9 were negative in IPZ.
Conclusions:
Activated human complements directly damage isolated guinea pig working hearts, and CD59 offers a significant protection against the injuries.
