PAFR-deficiency alleviates myocardial ischemia/reperfusion injury in mice via suppressing inflammation, oxidative stress and apoptosis

• Published in: Biochemical and biophysical research communications 2018-01, Vol.495 (4), p.2475-2481
• Main Authors: Wang, En-wei, Han, Yang-yang, Jia, Xu-sheng
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - immunology; Cytokines - immunology; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial injury; Myocardial Reperfusion Injury - immunology; Myocardial Reperfusion Injury - pathology; Myocarditis - immunology; Myocarditis - pathology; Oxidative stress; Oxidative Stress - immunology; PAFR; Platelet Membrane Glycoproteins - genetics; Platelet Membrane Glycoproteins - immunology; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - immunology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.12.132

Myocardial ischemia/reperfusion (I/R) still have high morbidity and mortality worldwide. Platelet activating factor (PAF) is a potent phospholipid regulator of inflammation. PAF acts on a single receptor (PAFR), which is expressed on cellular and nuclear membranes of various cell types. The study is aimed to explore if PAFR could modulate myocardial I/R injury in mice. PAFR expressions began to up-regulate at 1 h, and reached peak at 24 h. PAFR deletion markedly attenuated myocardial I/R injury, evidenced by the reduced infarct size and the improved cardiac function. Furthermore, PAFR-knockout inhibited inflammatory response, as demonstrated by down-regulated pro-inflammatory cytokines and chemokine, as well as the inactivation of nuclear factor κB (NF-κB). Additionally, PAFR-absence ameliorated oxidative stress induced by myocardial I/R, associated with the up-regulation of superoxide dismutase (SOD) and nuclear respiratory factor 2 (Nrf-2) activity. Finally, PAFR-deficiency impeded apoptosis, which was proved by the decreasing in terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL)-positive myocytes, and Caspase-3 cleavage. And the activation of Janus kinase 1-signal transducer and activator of transcription 1 (JAK1/STAT1) pathway was also suppressed by PAFR-knockout. The findings above were confirmed in lipopolysaccharide (LPS)-incubated cardiomyocytes with or without PAFR expressions in vitro. In summary, we supposed that inhibiting PAFR reduced inflammation, oxidative stress and apoptosis, and thus might be a promising therapeutic strategy to alleviate myocardial I/R injury. •PAFR expression was up-regulated in myocardial I/R model and affects cardiac function.•PAFR-absence reduces inflammation and oxidative stress in hearts of mice after I/R injury.•PAFR-deletion decreases JAK1/STAT1 pathway and alleviates apoptosis in hearts of mice after I/R.•PAFR-knockdown attenuates inflammation and oxidative stress, as well as suppresses apoptosis.