CTLA-4–Ig Therapy Preserves Cardiac Function Following Myocardial Infarction with the Reperfusion
DOI:
https://doi.org/10.7492/hmeknn95Keywords:
Myocardial infarction, CTLA-4-lg, T-cell costimulation, cytokines, cardioprotectionAbstract
Background:
Myocardial infarction (MI) induces reperfusion which prompts the strong inflammatory response contributing to the additional
myocardial injury, adverse remodeling and further degradation of cardiac performance. Immune checkpoint mechanisms, such as CTLA4 signaling, can have key functions in the regulation of T-cell stimulation and can be used as a therapeutic opportunity in the prevention
of post-ischemic inflammation.
Objective:
The objective of the study is to determine whether CTLA-4-Ig therapy has the potential of reducing inflammatory injury and preserving
cardiac function after myocardial infarction with reperfusion.
Method:
Murine ischemia-reperfusion injury model was created through the temporary ligation of the left anterior ascending coronary artery with
the subsequent reperfusion. Immediately following reperfusion, the mice were exposed to CTLA-4 -Ig or vehicle once more at 24 hours.
Echocardiography, histological evaluation of the size of infarcts, and a measurement of inflammatory biomarkers were used to measure
the cardiac structure and cardiac function, such as the presence of macrophage infiltration, and expression of cytokines.
Results:
Treatment of CTLA-4 Ig considerably lessened the inflammatory outcomes of post-reperfusion myocardial ischemia, as evidenced by the
significant decrease in the myocardial macrophage marker and pro-inflammatory cytokines. The mice that were treated had smaller
infarct areas, had left-ventricular ejection fraction, and ventricular dilation. The signs of negative remodeling such as fibrosis and
hypertrophy of the myocytes were also milded.
Conclusion:
The CTLA-4Ig therapy is effective in the prevention of the post-ischemic inflammatory injury and the maintenance of cardiac function
after reperfusion in myocardial infarction. Translational research is warranted by these findings to take immune checkpoint modulation as
a prospective cardioprotective approach
