scholarly journals GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Zhange Li ◽  
Honglin Xu ◽  
Xin Liu ◽  
Yang Hong ◽  
Han Lou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Transcription Factor ◽  
Heart Function ◽  
Heart Tissue ◽  
Chip Assay ◽  
Pyrin Domain ◽  
Important Regulator ◽  
Crucial Part ◽  
Oligomerization Domain

Abstract NLRP3 (Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3) inflammasome-mediated cardiomyocytes pyroptosis plays a crucial part in progression of acute myocardial infarction (MI). GDF11 (Growth Differentiation Factor 11) has been reported to generate cytoprotective effects in phylogenesis and multiple diseases, but the mechanism that GDF11 contributes to cardioprotection of MI and cardiomyocytes pyroptosis remains poorly understood. In our study, we first determined that GDF11 was abnormally downregulated in the heart tissue of MI mice and hypoxic cardiomyocytes. Moreover, AAV9-GDF11 markedly alleviated heart function in MI mice. Meanwhile, GDF11 overexpression also decreased the pyroptosis of hypoxic cardiomyocytes. PROMO and JASPAR prediction software found that transcription factor HOXA3 was predicted as an important regulator of NLRP3, and was confirmed by ChIP assay. Further analysis identifying GDF11 promoted the Smad2/3 pathway resulted in HOXA3 overexpression. Taken together, our study implies that GDF11 prevents cardiomyocytes pyroptosis via HOXA3/NLRP3 signaling pathway in MI mice.

scholarly journals Association of atrial arrhythmias with thrombospondin-1 in patients with acute myocardial infarction

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wenkai Liao ◽  
Li Xu ◽  
Yuxia Pan ◽  
Jie Wei ◽  
Peijia Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Heart Function ◽  
Coronary Intervention ◽  
Atrial Remodeling ◽  
Atrial Arrhythmias ◽  
Electrocardiographic Monitoring ◽  
Thrombospondin 1 ◽  
Independent Risk Factors ◽  
Hs Crp

Abstract Objectives Atrial remodeling is the main developmental cause of atrial arrhythmias (AA), which may induce atrial fibrillation, atrial flutter, atrial tachycardia, and frequent premature atrial beats in acute myocardial infarction (AMI) patients. Thrombospondin-1 (TSP-1) has been shown to play an important role in inflammatory and fibrotic processes, but its role in atrial arrhythmias is not well described. The purpose of this study was to investigate the role of TSP-1 in AMI patients with atrial arrhythmias. Methods A total of 219 patients with AMI who underwent percutaneous coronary intervention and with no previous arrhythmias were included. TSP-1 were analyzed in plasma samples. Patients were classified into 2 groups, namely, with and without AA during the acute phase of MI. Continuous electrocardiographic monitoring was used for AA diagnosis in hospital. Results Twenty-four patients developed AA. Patients with AA had higher TSP-1 levels (29.01 ± 25.87 μg/mL vs 18.36 ± 10.89 μg/mL, p < 0.001) than those without AA. AA patients also tended to be elderly (65.25 ± 9.98 years vs 57.47 ± 10.78 years, p < 0.001), had higher Hs-CRP (39.74 ± 43.50 mg/L vs 12.22 ± 19.25 mg/L, p < 0.001) and worse heart function. TSP-1 (OR 1.033; 95% CI 1.003–1.065, p = 0.034), Hs-CRP (OR 1.023; 95% CI 1.006–1.041, p = 0.008), age (OR 1.067; 95% CI 1.004–1.135, p = 0.038) and LVDd (OR 1.142; 95% CI 1.018–1.282, p = 0.024) emerged as independent risk factors for AA in AMI patients. Conclusion TSP-1 is a potential novel indicator of atrial arrhythmias during AMI. Graphical abstract

scholarly journals SUBCELLULAR LOCALIZATION OF FoxP3 TRANSCRIPTION FACTOR IN PATIENTS WITH ACUTE CORONARY SYNDROME: COMPARATIVE ANALYSIS AND PROSPECTIVE OBSERVATION

2021 ◽  
Vol 23 (4) ◽  
pp. 731-736
Author(s):  
I. V. Kologrivova ◽  
Tatiana E. Suslova ◽  
V. V. Ryabov ◽  
M. A. Shtatolkina ◽  
O. A. Koshelskaya ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Transcription Factor ◽  
T Lymphocytes ◽  
Subcellular Localization ◽  
Nuclear Localization ◽  
Mononuclear Cells ◽  
Nuclear Translocation ◽  
Coronary Syndrome ◽  
Treg Lymphocytes

The key cellular and molecular factors being involved in the resolution of inflammation following acute myocardial infarction remain poorly understood. T-regulatory (Treg) lymphocytes are characterized by the extreme potential to regulate the strength and direction of immune responses during the myocardial injury. The functional activity of Treg-lymphocytes depends upon the transcription factor forkhead box protein P3 (FoxP3). It may be also expressed in conventional T-lymphocytes at the stage of their activation. Nuclear localization of FoxP3 is a prerequisite factor determining its ability to impact the suppressive functions of Treglymphocytes.The aim of the present study was comparative evaluation of FoxP3+T-lymphocytes frequency and counts, combined with estimation of FoxP3 subcellular localization, in patients with acute myocardial infarction and chronic coronary syndrome and examination of changes of these parameters in the short-term follow-up of patients with myocardial infarction. The study included 14 patients with chronic coronary syndrome (8 males; 6 females; 63.2±9.0 y.o.) and 5 patients with acute anterior ST-segment elevation myocardial infarction (4 males; 1 female; 61.4±11.2 y.o.) at days 1, 3 and 7 after the event. The frequency of FoxP3+ conventional and regulatory T-lymphocytes was evaluated in peripheral blood mononuclear cells together with estimation of the level of FoxP3 nuclear localization by imaging flow cytometry.Patients with infarction were characterized by the decreased counts of FoxP3+Treg-lymphocytes compared to patients with chronic coronary syndrome, and exhibited even further decrease in the counts of FoxP3+Tregcells at day 7 after infarction, while frequency of Treg and conventional T-lymphocytes did not differ significantly. The level of FoxP3 nuclear translocation was lower both in Treg and conventional T-lymphocytes in patients at day 1 post-infarction compared to patients with chronic coronary syndrome. Absolute counts of FoxP3+Tregs with nuclear FoxP3 localization remained significantly lower both at days 1 and 7 post-infarction compared to patients with chronic coronary syndrome.Thus, here we demonstrated that FoxP3 nuclear localization experiences decrease in the course of acute myocardial infarction and may serve as a more sensitive marker of changes in Treg-lymphocyte functioning than simple evaluation of their frequency. 

scholarly journals Network pharmacology-based identification of major component of Angelica sinensis and its action mechanism for the treatment of acute myocardial infarction

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Xiaowei Niu ◽  
Jingjing Zhang ◽  
Jinrong Ni ◽  
Runqing Wang ◽  
Weiqiang Zhang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Er Stress ◽  
Heart Function ◽  
Network Pharmacology ◽  
Angelica Sinensis ◽  
Peroxisome Proliferator ◽  
Multiple Targets

Background: To decipher the mechanisms of Angelica sinensis for the treatment of acute myocardial infarction (AMI) using network pharmacology analysis. Methods: Databases were searched for the information on constituents, targets, and diseases. Cytoscape software was used to construct the constituent–target–disease network and screen the major targets, which were annotated with the DAVID (Database for Annotation, Visualization and Integrated Discovery) tool. The cardioprotective effects of Angelica sinensis polysaccharide (ASP), a major component of A. sinensis, were validated both in H9c2 cells subjected to simulated ischemia by oxygen and glucose deprivation and in rats with AMI by ligation of the left anterior coronary artery. Results: We identified 228 major targets against AMI injury for A. sinensis, which regulated multiple pathways and hit multiple targets involved in several biological processes. ASP significantly decreased endoplasmic reticulum (ER) stress-induced cell death both in vitro and in vivo. In ischemia injury rats, ASP treatment reduced infarct size and preserved heart function. ASP enhanced activating transcription factor 6 (ATF6) activity, which improved ER-protein folding capacity. ASP activated the expression of p-AMP-activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α). Additionally, ASP attenuated levels of proinflammatory cytokines and maintained a balance in the oxidant/antioxidant levels after AMI. Conclusion:In silico analysis revealed the associations between A. sinensis and AMI through multiple targets and several key signaling pathways. Experimental data indicate that ASP protects the heart against ischemic injury by activating ATF6 to ameliorate the detrimental ER stress. ASP’s effects could be mediated via the activation of AMPK-PGC1α pathway.

scholarly journals Clinical Study of The Early Application of Lvabradine For Acute Anterior Myocardial Infarction Patients After PCI With Early Heart Failure To Observe Cardiac Function And Prognosis

2021 ◽  
Author(s):  
Jun-Qing Gao ◽  
Xu wang ◽  
Ling-Yan Li ◽  
Hua Zhang ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Heart Function ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Anterior Myocardial Infarction ◽  
Standard Drug ◽  
End Diastolic Volume ◽  
Percutaneous Coronary

Abstract BackgroundThe incidence of acute myocardial infarction is increasing each year. Percutaneous coronary intervention has become highly preferred for patients with acute myocardial infarction because it not traumatic and improves heart function. However, the mortality and disability rates are still high. For the first time, we used ivabradine in patients with acute anterior myocardial infarction. We expect that this new method will enhance heart function and clinical prognosis because of heart rate control, decreases in heart preload and improvements in left ventricular end-diastolic volume.Method and analysisThis is a prospective, randomized, controlled, open-label, multicenter and optimally designed clinical trial. A total of 500 patients with acute anterior myocardial infarction after Percutaneous coronary intervention（PCI）with early heart failure will be enrolled. Eligible subjects will be randomized at a 1:1 ratio to take the standard drug treatment or receive the standard drug treatment plus ivabradine. The primary outcome measure is left ventricular end-diastolic volume. Left ventricular ejection fraction, adverse cardiac events, and the Canadian angina pectoris score will be evaluated as secondary endpoints. Blood biochemical testing will be used as the safety endpoints. Ethics and dissemination The clinical research will be carried out in strict accordance with the relevant Chinese laws and regulations, the Declaration of Helsinki, and the ethical and scientific principles stipulated by the Chinese GCP. All participants will provide informed consent. The personal information of patients will be kept confidential. Findings from the trial will be disseminated through peer-reviewed journals and scientific conferences.ClinicalTrials.govID:ChiCTR2000032731,Registered8May,2020 http://www.chictr.org.cn/showproj.aspx?proj=53275 Trial Statusversion number: Protocol version 1.0., approved9 May，2020Trial ongoingStudy execute time: From 1 September 2020 to 31 Octomber 2022Recruiting time: From 8 May 2020 to 31 December 2022

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