The PD-1 with PD-L1 Axis Is Pertinent with the Immune Modulation of Atrial Fibrillation by Regulating T Cell Excitation and Promoting the Secretion of Inflammatory Factors.

Objective: To analyze the role of PD-1/PD-L1 signaling pathway in regulating T cell activation and secretion of proinflammatory factors in atrial fibrillation. Methods: Forty-five patients with atrial fibrillation admitted to the cardiology department of our hospital from July 2019 to March 2021 were selected to be included in the atrial fibrillation group, and another 45 healthy volunteers were selected as the control group to compare the changes of T cell CD69 and human leukocyte antigen-DR (HLA-DR) expression in the peripheral blood of the two study groups; compare the changes of programmed death factor-1 on CD4+ and CD8+ lymphocytes in the peripheral blood of the two groups (PD-1) expression changes and PD-L1 and PD-L2 expression changes on peripheral blood myeloid dendritic cells (mDCs) cells; compare the changes of interleukin-2, interleukin-6, interleukin-10, and interleukin-17A (IL-2, IL-6, IL-10, and IL-17), tumor necrosis factor (TNF), and interferon gamma (IFN-γ) concentrations on peripheral blood inflammatory factors in the two groups; and isolate the two groups of peripheral blood mDCs cells; α interferon upregulated PD-L1 expression in the cells and analyzed the effect of PD-L1 expression on the ability of mDCs to stimulate T cells to secrete cytokines. Results: The positive expression rates of CD69 and HLA-DR on peripheral blood CD3+ T lymphocytes were significantly higher in patients in the atrial fibrillation group than in the control group, and the differences were statistically significant (P < 0.01). The positive expression rate of PD-1 on CD4+ lymphocytes was significantly lower in patients in the atrial fibrillation group than in the control group (P < 0.01). There was no statistically significant difference between the two groups in terms of PD-1 positive expression rate on CD8+ lymphocytes (P > 0.05). The positive expression rate of PD-L1 on mDCs cells was significantly lower in patients in the atrial fibrillation group than in the control group (P < 0.01), and there was no statistically significant difference between the two groups in the positive expression rate of PD-L2 on mDCs cells, PD-L1, and PD-L2 on CD4+ and CD8+ T cells (P > 0.05). The concentrations of IL-2, IL-6, IL-10, and IFN-γ in peripheral blood were significantly higher in patients in the atrial fibrillation group than in the control group (P < 0.05), and there was no statistically significant difference in the comparison of IL-17A and TNF concentrations in peripheral blood between the two groups (P > 0.05). In the atrial fibrillation group, the ability of mDCs to stimulate T cells to secrete IL-2 and IFN-γ was significantly higher, and the ability to secrete IL-10 was significantly lower compared with the control group (P < 0.05). After α interferon upregulated PD-L1 expression in cells, the ability of mDCs to stimulate T cells to secrete IL-2, IL-10, and IFN-γ cytokines was reversed in patients in the atrial fibrillation group, and the differences compared with the control group were not statistically significant (P > 0.05). Conclusion: PD-1/PD-L1 signaling pathway may play an immunomodulatory role in the pathogenesis of atrial fibrillation by promoting increased secretion of inflammatory factors through regulating T cell activation.

Generation of a human iPSC line CIBi009-A from a patient with familial hypercholesterolemia carrying variants of LDLR c.T1241G and APOB c.G1618T.

Patients with familial hypercholesterolemia (FH) are susceptible to premature coronary artery disease. We generated a human iPSC line CIBi009-A from a patient with FH who carried variants of LDLR c.T1241G and APOB c.G1618T. This line will be a valuable resource for investigating novel therapeutic approaches to FH.

Effects of probucol on contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention.

OBJECTIVE: This study was performed to explore the effects of probucol on contrast-induced acute kidney injury (CIAKI) in patients with coronary heart disease undergoing percutaneous coronary intervention (PCI). METHODS: In total, 220 patients undergoing PCI were randomly assigned to either the control group (hydration from 12 hours before to 12 hours after contrast administration; n = 110) or the probucol group (hydration plus probucol 500 mg twice daily 1 day before and 3 days after the operation; n = 110). The primary endpoint was the occurrence of serum creatinine (Scr)-based CIAKI, defined as an absolute increase in Scr by 0.5 mg/dl (44.2 µmol/L) or a relative 25% increase from baseline within 48 to 72 hours after exposure to contrast medium. The secondary outcomes were composite variations in Scr, blood urea nitrogen (BUN), creatinine clearance rate (Ccr) within 48 to 72 hours, and major adverse events during hospitalization or the 7-day follow-up period after PCI. RESULTS: The overall incidence of Scr-based CIAKI was 7.3% (16/220): 5.5% (6/110) in the control group and 9.1% (10/110) in the probucol group (χ = 1.078, P = .298). There were no significant differences in the occurrence rate of major adverse events during hospitalization or the 7-day follow-up period after PCI between the groups. Multivariate logistic regression analysis showed that probucol was not an independent protective factor for CIAKI (odds ratio, 1.825; 95% confidence interval, 0.639-5.212; P = .261). However, hydration was an independent protective factor (odds ratio, 0.997; 95% confidence interval, 0.995-0.999; P = .004). CONCLUSION: Probucol cannot effectively reduce the incidence of CIAKI through its anti-inflammatory and antioxidative stress effects.