Overexpression of genes involved in lymphocyte activation and regulation are associated with reduced CRM-derived cardiac remodelling after STEMI

• Published in: International immunopharmacology Vol. 95; p. 107490
• Main Authors: de Dios, Elena, Rios-Navarro, César, Pérez-Solé, Nerea, Gavara, Jose, Marcos-Garcés, Victor, Forteza, Maria J., Oltra, Ricardo, Vila, José M., Chorro, Francisco J., Bodi, Vicente
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2021; Elsevier BV
• Subjects: Antigens; Apoptosis; CD25 antigen; CD69 antigen; Cell activation; Clinical trials; Confidence intervals; CTLA-4 protein; Cytotoxicity; Gene expression; Genes; Heart; Immune checkpoint; Immunomodulation; Immunoregulation; Leukocytes (mononuclear); Lymphocyte; Lymphocytes; Lymphocytes T; Lymphopenia; Magnetic resonance; Myocardial infarction; PD-1 protein; Peripheral blood mononuclear cells; Regression analysis; Reperfusion; Statistical analysis; Structure-function relationships; Transcription activation; Ventricle; Ventricular remodelling; Myocardial infarction; IL; LVESVI; LVEF; CMR; LV; PBMCs; LVEDVI; LAG-3; PCI; STEMI; CTLA-4; TIGIT; TIM-3; Ventricular remodelling; PD-1; Lymphocyte
• DOI: 10.1016/j.intimp.2021.107490
• ISSN: 1567-5769; 1878-1705

•Uncontrolled immune response after STEMI correlates with deleterious cardiac events.•Genes involved in lymphocyte activation and regulation are altered following STEMI.•Overexpression of immune checkpoints correlates with reduced infarct size.•Exploring therapies aimed at these checkpoints would be very useful in the future.•Increased CD25 expression is associated with better cardiac structure and function. Lymphopenia after ST-segment elevation myocardial infarction (STEMI) correlates with deleterious cardiac consequences and worse prognosis. An in-depth examination of genes implicated in lymphocyte proliferation, activation and regulation and their association with short- and long-term cardiac structure and function is therefore of great interest. Peripheral blood mononuclear cells were isolated from 10 control subjects and 64 patients with a first STEMI treated with primary percutaneous coronary intervention and submitted to cardiac magnetic resonance after 1 week and 6 months. mRNA expression of genes implicated in lymphocyte activation (CD25 and CD69) and regulation [programmed death (PD)-1 and cytotoxic T-lymphocyte antigen (CTLA)-4] were determined by qRT-PCR. In comparison to controls, STEMI patients showed heightened mRNA expression of CD25 and lower PD-1 and CTLA-4 96 h after coronary reperfusion. Patients with extensive infarctions (>30% of left ventricular mass) at 1 week displayed a notable reduction in CD25, CD69, PD-1, and CTLA-4 expression (p < 0.05). However, CD25 was the only predictor of 1-week extensive infarct size in multivariate logistic regression analysis (odds ratio 0.019; 95% confidence interval [0.001–0.505]; p = 0.018). Regarding long-term ventricular function, mRNA expression of CD25 under the mean value was associated with worse ventricular function and more adverse remodelling. Following STEMI, heightened expression of genes expressed in regulatory T cells (CD25 and CD69) and immune checkpoints (PD-1 and CTLA-4) correlates with a better short- and long-term cardiac structure and function. Advancing understanding of the pathophysiology of lymphopenia and evaluating novel immunomodulatory therapies will help translate these results into future clinical trials.