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Objective Little is currently known on the role of T-cell immunoglobulin and ITIM domain (TIGIT) expression in Foxp3+ regulatory T cells (TIGIT+Tregs) in acute coronary syndrome (ACS) patients. The aim of this study was to investigate the role and alterations of TIGIT+Tregs in ACS patients. Methods We enrolled 117 subjects, including 61 ACS patients, 26 chronic coronary syndrome (CCS) patients, and 30 control subjects without coronary artery disease. The quantification of TIGIT+Tregs was determined by flow cytometry; serum interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) were also measured. Results TIGIT+Tregs expression was significantly lower in ACS patients compared with CCS and control patients (P<0.05). The expression of TIGIT+Tregs was comparable in patients with and without traditional risk factors (P>0.05). Logistic regression analysis revealed that TIGIT+Tregs levels are independent predictors of ACS (P<0.01). Receiver-operating characteristic (ROC) curve analysis showed the expression levels of TIGIT+Tregs had a discriminative power for ACS (P<0.01). IL-6 levels were increased (P<0.01), while TGF-β was decreased in ACS patients compared with CCS and control patients (P<0.01). Meanwhile, an inverse correlation between IL-6 and TIGIT+Tregs was observed (P<0.01), while a positive correlation between TGF-β and TIGIT+Tregs was found (P<0.05). Conclusion TIGIT+Tregs levels are significantly reduced in ACS, accompanied by upregulated IL-6 and downregulated TGF-β expression. The downregulated TIGIT+Tregs are independent predictors of ACS. These findings suggest that TIGIT+Tregs may have an anti-inflammatory and protective effect on ACS, and its decreased expression may be associated with atherosclerotic plaque destabilization.

Background and Aim: This study aims to investigate the effect and mechanism of proprotein convertase subtilisin/Kexin type 9 (PCSK9) on myocardial ischemia-reperfusion injury (MIRI) and provide a reference for clinical prevention and treatment of acute myocardial infarction (AMI).METHODS: We established a rat myocardial ischemia/reperfusion (I/R) model and AC16 hypoxia/reoxygenation (H/R) model. A total of 48 adult male Sprague-Dawley rats were randomly assigned to three groups (n=16): control, I/R, and I/R +SiRNA. In I/R and I/R +siRNA groups, myocardial ischemia was induced via occlusion of the left anterior descending branch (LAD) of the coronary artery in rats in I/R group for 0.5 h and reperfused for three days. To assess the myocardial injury, the rats were subjected to an electrocardiogram (ECG), cardiac function tests, cardiac enzymes analysis, and 2,3,5triphenyl tetrazolium chloride (TTC)/Evan Blue (EB) staining. Meanwhile, hematoxylin-eosin (HE) staining was used to detect morphological changes in cardiomyocytes in each group, and the level of myocardial brosis was quanti ed using Masson trichrome staining. Differences in the expression of autophagylevel proteins and Bcl-2/adenovirus E1B 19-kDa interacting protein (Bnip3) signaling-related proteins were determined by protein blotting. RESULTS: I/R and H/R injury increased the expression level of PCSK9, activated the downstream Bnip3, and subsequently triggered autophagy. In vitro and in vivo experimental studies revealed that siRNA knockdown of PCSK9 resulted in reduced expression of the autophagic protein Beclin-1, light chain 3 (LC3) compared to normal control-treated cells and control-operated groups. Simultaneously, the presentation of the autophagic pathway Bnip3 was downregulated. Furthermore, PCSK9-mediated small interfering RNA (siRNA) group injected into the left ventricular wall signi cantly improved cardiac function and myocardial infarct size, as well as the expression of mRNA of Recombinant Human Interleukin-1β IL-1β. Moreover, Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)was signi cantly downregulated and reduced the in ammatory response compared with the I/R group.CONCLUSIONS: In ischemic/hypoxic circumstances, PCSK9 expression was dramatically increased. PCSK9 knockdown alleviated MIRI via the Bnip3-mediated autophagic pathway and improved in ammatory response, myocardial infarct size, and cardiac function.