Longitudinal Variations in Th and Treg Cells Before and After Percutaneous Coronary Intervention, and Their Intercorrelations and Prognostic Value in Acute Syndrome Patients.

T helper (Th) and regulatory T (Treg) cells regulate atherosclerosis, plaque, inflammation to involve in acute coronary syndrome (ACS). The current study aimed to investigate the clinical implications of Th and Treg cells in ACS patients receiving percutaneous coronary intervention (PCI). Blood Th1, Th2, Th17 and Treg cells were detected in 160 ACS patients before PCI, after PCI, at 1 month (M). Short physical performance battery (SPPB) at M1/M3 and major adverse cardiac event (MACE) during follow-ups were evaluated. Th1 and Th17 both showed upward trends during PCI, then greatly declined at M1 (P < 0.001). Th2 exhibited an upward trend during PCI but decreased slightly at M1 (P < 0.001). Treg remained stable during PCI but elevated at M1 (P < 0.001). Moreover, a positive correlation between Th1 and Th17, a negative correlation between Th17 and Treg, were discovered at several timepoints (most P < 0.050). Interestingly, the receiver operating curve (ROC) analyses revealed that Th1 [area under curve (AUC) between 0.633-0.645] and Th17 (AUC between 0.626-0.699) exhibited values estimating SPPB score <= 6 points at M1 or M3 to some extent. Importantly, Th1 (AUC between 0.708-0.710), Th17 (AUC between 0.694-0.783), and Treg (AUC between 0.706-0.729) predicted MACE risk. Multivariate models involving Th and Treg cells along with other characteristics revealed acceptable values estimating SPPB score <= 6 points at M1 or M3 (AUC between 0.690-0.813), and good values predicting MACE risk (AUC between 0.830-0.971). Dynamic variations in Th and Treg cells can predict the prognosis of ACS patients receiving PCI.

JNK Pathway-Associated Phosphatase Deficiency Facilitates Atherosclerotic Progression by Inducing T-Helper 1 and 17 Polarization and Inflammation in an ERK- and NF-κB Pathway-Dependent Manner.

AIM: JNK pathway-associated phosphatase (JKAP) regulates T cell-mediated immunity and inflammation, which are involved in atherosclerosis pathogenesis. This study investigated the effects of JKAP on T-helper (Th) cell polarization, inflammation, and atherosclerotic progression. METHODS: Serum JKAP levels were measured in 30 patients with coronary heart disease (CHD) and 30 controls. CHD blood naïve CD4＋ T cells were acquired, followed by JKAP overexpression and knockdown with or without treatment with PD98059 (ERK inhibitor) or BAY-11-7082 (NF-κB inhibitor) in vitro. CD4＋ T-cell conditional JKAP ablation mice were established in vivo, followed by the construction of an atherosclerosis model. RESULTS: JKAP was reduced and negatively correlated with the Gensini score, CRP, Th1 cells, Th17 cells, and proinflammatory cytokines in patients with CHD. In vitro, JKAP overexpression suppressed Th1 and Th17 cell differentiation and proinflammatory cytokines, whereas JKAP knockdown exerted the opposite effect; however, JKAP modification did not affect Th2 cell differentiation. Interestingly, JKAP negatively regulated the ERK and NF-κB pathways; meanwhile, the PD98059 and BAY-11-7082 treatments repressed Th1 and Th17 cell differentiation, and attenuated the effect of JKAP knockdown on these indices. In vivo, conditional CD4＋ T-cell JKAP ablation increased Th1 and Th17 cell polarization in the spleen, lymph node, blood, and/or aortic root. Furthermore, CD4＋ T-cell conditional JKAP ablation exaggerated atherosclerotic lesions in the aorta, elevated CD4+ cell infiltration and proinflammatory cytokines in the aortic root, and activated the ERK and NF-κB pathways in the aortic root. CONCLUSION: JKAP ablation facilitates atherosclerosis progression by promoting Th1 and 17 polarization and inflammation through regulation of the ERK and NF-κB pathways.

Impact of post-dilatation on post-procedural physiology, microcirculatory resistance, and target vessel failure in STEMI patients undergoing PPCI: A single-center experience.

BACKGROUND: Suboptimal stent deployment is frequently observed in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). This study sought to investigate whether these patients could benefit from post-dilatation with respect to post-procedural physiology, microcirculatory resistance, and long-term clinical outcomes. METHODS: This was a retrospective study of consecutive STEMI patients who underwent successful stent implantation during PPCI from February 2016 to November 2021. Post-procedural physiology and microcirculatory resistance were assessed by Murray law-based quantitative flow ratio (µQFR) and angiographic microcirculatory resistance (AMR), respectively. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel-oriented myocardial infarction, and clinically driven target vessel revascularization. RESULTS: A total of 671 patients (671 culprit vessels) were included. Post-dilatation was selectively performed in 430 (64.1%) culprit vessels, resulting in a 0.02 (interquartile range: 0.00-0.05, p < 0.001) increase in post-procedural µQFR but no significant impact on AMR. During a median follow-up of 2.8 years (interquartile range: 1.4-3.0 years), TVF occurred in 47 (7.0%) patients. Post-dilatation demonstrated a trend toward a reduction in TVF (5.3% vs. 10.0%; adjusted hazard ratio: 0.60, 95% confidence interval: 0.33-1.09, p = 0.094), mainly driven by a lower incidence of clinically driven target vessel revascularization (1.6% vs. 4.1%; adjusted hazard ratio: 0.32, 95% confidence interval: 0.11-0.90, p = 0.030). CONCLUSIONS: In STEMI patients undergoing PPCI, selective post-dilatation was associated with improved post-procedural physiological results and a trend toward less TVF events without aggravating microcirculatory resistance.