Effect of Tegretol on Oxidative Stress, Serum Inflammatory Factors, and Left Ventricular Function in AMI Patients after Emergency PCI.

To investigate the effects of tegretol on oxidative stress, serum inflammatory factors, and left ventricular function in patients with acute myocardial infarction (AMI) after emergency percutaneous coronary intervention (PCI), 70 AMI patients who received PCI in the emergency department of our hospital from January 2021 to December 2021 were collected. The patients in the control group were treated with aspirin, clopidogrel, and heparin sodium during the perioperative period, and the patients in the study group were treated with tegretol. The levels of oxidative stress, serum inflammatory factors, and left ventricular function index were compared between the two groups. The patients in the control group were treated with TT ((12.00 ± 2.05) s), APTT ((35.50 ± 4.19) s), PT ((16.60 ± 1.58) s), TT ((15.90 ± 2.14) s) APTT ((30.40 ± 3.80) s), and PT ((14.30 ± 1.45) s)) and were comparable (P > 0.05), and the difference was statistically significant (t = 8.210, 4.600, 7.010, P < 0.001). There was no comparable difference in the level of oxidative stress index before treatment (P > 0.05). After treatment, there was significant difference in MDA ((14.53 ± 2.14) mmol/L), SOD ((120.45 ± 8.17) U/L), MDA ((11.15 ± 2.02) mmol/L), and SOD ((129.86 ± 8.55) U/L) in the control group (t = 7.320, 5.099, P < 0.001). The levels of inflammatory factors in patients before treatment were not comparable (P > 0.05). After treatment, there were levels of IL-6 ((3.20 ± 1.05) ng/L), CRP ((4.80 ± 1.16) mg/L), MPO ((196.78 ± 21.51) mg/L) and TNF-α ((3.96 ± 0.80) pmol/L), IL-6 ((1.95 ± 0.80) ng/L), CRP ((3.10 ± 1.02) mg/L), MPO ((163.60 ± 21.10) mg/L), and TNF-α in a study group level ((3.05 ± 0.70) pmol/L), with statistically significant difference (t = 5.187, 6.028, 6.031, 4.689,P < 0.001). Before treatment, there was no comparable difference in the level of left ventricular function index (P > 0.05). After treatment, there was significant difference in LVEF ((46.10 ± 2.39) %) and LVDD ((52.06 ± 1.07) mm), LVEF ((56.85 ± 2.33) %), and LVDD ((48.75 ± 1.02) mm) in the control group (t = 17.640, 21.540, P < 0.001). Tegretol as an adjunctive therapy for emergency PCI patients with acute myocardial infarction can effectively improve postoperative coagulation function, reduce oxidative stress and inflammatory reaction, and improve cardiac function indicators. It has a positive clinical value.

Farnesyl diphosphate synthase regulated endothelial proliferation and autophagy during rat pulmonary arterial hypertension induced by monocrotaline.

BACKGROUND: The proliferation ability and autophagy level of pulmonary artery endothelial cells (PAECs) play an important role in promoting the development of pulmonary artery hypertension (PAH), and there is still no effective treatment for PAH. Farnesyl diphosphate synthase (FDPS) is a key enzyme in the mevalonate pathway. The intermediate metabolites of this pathway are closely related to the activity of autophagy-associated small G proteins, including Ras-related C3 botulinum toxin substrate 1 (Rac1). Studies have shown that the mevalonate pathway affects the activation levels of different small G proteins, autophagy signaling pathways, vascular endothelial function, and so on. However, the exact relationship between them is still unclear in PAH. METHOD: In vitro, western blotting and mRFP-GFP-LC3 puncta formation assays were used to observe the expression of FDPS and the level of autophagy in PAECs treated with monocrotaline pyrrole (MCTP). In addition, cell proliferation and migration assays were used to assess the effect of FDPS on endothelial function, and Rac1 activity assays were used to evaluate the effect of Rac1 activation on PAEC autophagy via the PI3K/AKT/mTOR signaling pathway. In vivo, the right heart catheterization method, hematoxylin and eosin (H&E) staining and western blotting were used to determine the effect of FDPS on PAEC autophagy and monocrotaline (MCT)-induced PAH. RESULTS: We show that the expression of FDPS is increased in the PAH module in vitro and in vivo, concomitant with the induction of autophagy and the activation of Rac1. Our data demonstrate that inhibition of FDPS ameliorates endothelial function and decreases MCT-induced autophagy levels. Mechanistically, we found that FDPS promotes autophagy, Rac1 activity and endothelial disfunction through the PI3K/AKT/mTOR signaling pathway. CONCLUSION: Our study suggests that FDPS contributes to active small G protein-induced autophagy during MCT-induced PAH, which may serve as a potential therapeutic target against PAH.

Transcriptome analysis uncovers the autophagy-mediated regulatory patterns of the immune microenvironment in dilated cardiomyopathy.

The relationship between autophagy and immunity has been well studied. However, little is known about the role of autophagy in the immune microenvironment during the progression of dilated cardiomyopathy (DCM). Therefore, this study aims to uncover the effect of autophagy on the immune microenvironment in the context of DCM. By investigating the autophagy gene expression differences between healthy donors and DCM samples, 23 dysregulated autophagy genes were identified. Using a series of bioinformatics methods, 13 DCM-related autophagy genes were screened and used to construct a risk prediction model, which can well distinguish DCM and healthy samples. Then, the connections between autophagy and immune responses including infiltrated immunocytes, immune reaction gene-sets and human leukocyte antigen (HLA) genes were systematically evaluated. In addition, two autophagy-mediated expression patterns in DCM were determined via the unsupervised consensus clustering analysis, and the immune characteristics of different patterns were revealed. In conclusion, our study revealed the strong effect of autophagy on the DCM immune microenvironment and provided new insights to understand the pathogenesis and treatment of DCM.