Interleukin-38 ameliorates myocardial Ischemia-Reperfusion injury via inhibition of NLRP3 inflammasome activation in fibroblasts through the IL-1R8/SYK axis.

Objective: Although IL-38 is recognized for its regulatory role in a spectrum of chronic inflammatory diseases, investigations into its cardiac physiological and pathophysiological functions are nascent. Our aim was to delineate the biological impact of IL-38 in the context of myocardial ischemia-reperfusion injury (MIRI) and to uncover the mechanisms through which it exerts its effects.

Methods And Results: In this study, we used an MIRI mouse model, LPS/ATP stimulation, and a hypoxia/reoxygenation cell model to determine the regulatory influence of IL-38 on MIRI.

Primary Aldosteronism Influences Cardiac Structure, Function, and Disease Risk: Evidence From Mendelian Randomization Analysis.

Although observational studies have linked primary aldosteronism (PA) with cardiovascular diseases (CVDs), the causality remains uncertain. In this study, we aimed to investigate whether PA is causally associated with CVD risk and cardiac magnetic resonance (CMR) parameters using the Mendelian randomization (MR) method. Independent and genome-wide significant single nucleotide polymorphisms for PA were extracted from genome-wide association study (GWAS) summary statistics.

IL-4-Induced Gene 1: A Potential Player in Myocardial Infarction.

Myocardial infarction (MI), a severe outcome of cardiovascular disease, poses a serious threat to human health. Uncontrolled inflammation and excessive cardiomyocyte death, following an infarction event, significantly contribute to both the mortality rate and complications associated with MI. The protein IL-4-induced gene 1 (IL4I1 or FIG1) serves as a natural inhibitor of innate and adaptive immunity, playing a crucial role in CD4+ T cell differentiation, macrophage polarization, and ferroptosis inhibition.

Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study.

Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of T2D with CAVS and the mediating effects of circulating metabolites and blood pressure using genome-wide association study (GWAS) summary statistics. The inverse variance weighted (IVW) method was used for the primary MR analysis, and comprehensive sensitivity analyses were performed to validate the robustness of the results.

Latency-associated peptide (LAP)CD4 regulatory T cells prevent atherosclerosis by modulating macrophage polarization.

Rationale: A persistent autoimmune and inflammatory response plays a critical role in the progression of atherosclerosis. The transcription factor forkhead box P3 (Foxp3)CD4 regulatory T cells (Foxp3 Tregs) attenuate atherosclerosis. Latency-associated peptide (LAP)CD4 T cells are a new class of Tregs whose role in atherosclerosis is unknown.

Case report: Malignant vasovagal reflex syndrome during percutaneous transcatheter closure of patent foramen ovale.

Malignant vasovagal reflex syndrome can be induced by pulling of cardiac tissue during percutaneous transcatheter closure of patent foramen ovale. In this case, a patient presented with a malignant vasovagal reflex syndrome characterized by decreased heart rate, cardiac arrest, and ventricular tachycardia. Therefore, it's particularly important to observe patients' heart rate and timely deal with vasovagal reflex syndrome during the operation.

Ablation of CXCR4 expression in cardiomyocytes exacerbates isoproterenol‑induced cell death and heart failure.

CXCR4 is a seven‑transmembrane‑spanning Gi‑coupled receptor for the SDF‑1 chemokine and plays a critical role in cardiovascular development and post‑injury repair. However, the specific role of CXCR4 in cardiomyocytes is incompletely understood. It was hypothesized that CXCR4 activation in cardiomyocytes antagonizes β‑adrenoceptor/Gs signaling‑induced cardiac dysfunction.

Interleukin-27 Ameliorates Atherosclerosis in ApoE Mice through Regulatory T Cell Augmentation and Dendritic Cell Tolerance.

Atherosclerosis, which is characterized by chronic inflammation in the arterial wall, is driven by immune cells and cytokines. Recent evidence indicated that interleukin (IL)-27 showed pleiotropic properties in immune diseases. However, precise mechanisms of IL-27, especially in atherosclerosis remains unknown.

Effects of IL-38 on Macrophages and Myocardial Ischemic Injury.

Macrophages play an important role in clearing necrotic myocardial tissues, myocardial ischemia-reperfusion injury, and ventricular remodeling after myocardial infarction. M1 macrophages not only participate in the inflammatory response in myocardial tissues after infarction, which causes heart damage, but also exert a protective effect on the heart during ischemia. In contrast, M2 macrophages exhibit anti-inflammatory and tissue repair properties by inducing the production of high levels of anti-inflammatory cytokines and fibro-progenitor cells.

IL-37 Expression in Patients with Abdominal Aortic Aneurysm and Its Role in the Necroptosis of Vascular Smooth Muscle Cells.

Background: Our previous studies have shown that interleukin- (IL-) 37 plays a protective role in patients and animal models with coronary artery disease. However, the role of IL-37 in patients with abdominal aortic aneurysm (AAA), another artery disease, is yet to be elucidated.

Methods And Results: AAA tissues and plasma samples were obtained from patients with or without surgical intervention.

Role of IL-37- and IL-37-Treated Dendritic Cells in Acute Coronary Syndrome.

As a chronic inflammatory disease, atherosclerosis is a leading cause of morbidity and mortality in most countries. Inflammation is responsible for plaque instability and the subsequent onset of acute coronary syndrome (ACS), which is one of the leading causes of hospitalization. Therefore, exploring the potential mechanism underlying ACS is of considerable concern, and searching for alternative therapeutic targets is very urgent.

GARP and GARP-Treated tDC Prevented the Formation of Atherosclerotic Plaques in ApoE Mice.

Purpose: This study aims to clarify the specific mechanism by which GARP affects the atherosclerotic plaques in ApoE mice and the effect of GARP-tDC on atherosclerosis.

Methods: The mice were randomly divided into three groups: the control group, the GARP-overexpressed group and the GARP-inhibited group. After 12 weeks, all the mice were euthanized, and the specimens were collected.

Corrigendum: Galectin-9: A Suppressor of Atherosclerosis?

[This corrects the article DOI: 10.3389/fimmu.2020.

Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE Mice.

Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to antigens, including oxidized low-density lipoprotein (oxLDL) and phosphorylcholine (PC). Dendritic cells (DCs), which are antigen-presenting cells that activate T cells, are present in atherosclerotic lesions and are activated in immune organs. However, the mechanism by which PC promotes atherosclerosis is unclear.

The Long Noncoding RNA Hotair Regulates Oxidative Stress and Cardiac Myocyte Apoptosis during Ischemia-Reperfusion Injury.

Oxidative stress and subsequent cardiac myocyte apoptosis play central roles in the initiation and progression of myocardial ischemia-reperfusion (I/R) injury. Homeobox transcript antisense intergenic RNA () was previously implicated in various heart diseases, yet its role in myocardial I/R injury has not been clearly demonstrated. Mice with cardiac-restricted knockdown or overexpression of were exposed to I/R surgery.

Interleukin-38 alleviates cardiac remodelling after myocardial infarction.

Excessive immune-mediated inflammatory reaction plays a deleterious role in ventricular remodelling after myocardial infarction (MI). Interleukin (IL)-38 is a newly characterized cytokine of the IL-1 family and has been reported to exert a protective effect in some autoimmune diseases. However, its role in cardiac remodelling post-MI remains unknown.

IL-37 Plays a Beneficial Role in Patients with Acute Coronary Syndrome.

Background: Interleukin-37 (IL-37) acts as an inhibitor of innate and adaptive immunity. However, the exact role of IL-37 in the patients with acute coronary syndrome (ACS) remains to be elucidated.

Methods: Patients were classified into 4 groups: normal coronary artery (NCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI).

The IL-2/Anti-IL-2 Complex Attenuates Cardiac Ischaemia-Reperfusion Injury Through Expansion of Regulatory T Cells.

Background/aims: Regulatory T cells (Tregs) can suppress immunologic damage in myocardial ischaemia/reperfusion injury (MIRI), however, the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate MIRI in mice.

Methods: Myocardial I/R was surgically induced in male C57BL/6 mice, aged 8-10 weeks, that were randomly assigned to 1) sham group (Sham), 2) Phosphate Buffered Saline (PBS), 3) IL-2-anti-IL-2 Ab complex (IL-2C), or 4) sham group, 5) PBS, 6) IL-2C after MIRI, or 7) IL-2C, 8) IL-2C+anti-CD25 mAbs, or 9) IL-2C; 10) IL-2C+anti-TGF-β1 mAbs, 11) IL-2C+anti-IL-10 mAbs.

Exogenous interleukin 37 ameliorates atherosclerosis via inducing the Treg response in ApoE-deficient mice.

Our previous study indicated that interleukin (IL)-37 is involved in atherosclerosis. In the present study, Anterior tibial arteries were collected from diabetes patients and controls. A histopathological analysis showed that IL-37 was over-expressed in human atherosclerotic plaques.

CD4 CD25 GARP regulatory T cells display a compromised suppressive function in patients with dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein A repetitions predominant (GARP) expressed on activated CD4 T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4  CD25  GARP regulatory T (Treg) cells in DCM.

Interleukin-37 and Dendritic Cells Treated With Interleukin-37 Plus Troponin I Ameliorate Cardiac Remodeling After Myocardial Infarction.

Background: Excessive immune-mediated inflammatory reactions play a deleterious role in postinfarction ventricular remodeling. Interleukin-37 (IL-37) emerges as an inhibitor of both innate and adaptive immunity. However, the exact role of IL-37 and IL-37 plus troponin I (TnI)-treated dendritic cells (DCs) in ventricular remodeling after myocardial infarction (MI) remains elusive.

Increased IL-37 concentrations in patients with arterial calcification.

Background: Our previous study indicates that IL-37 plays a critical role in both atherosclerosis and arterial calcification. However, whether IL-37 concentrations are significantly changed in patients with arterial calcification has not yet been investigated.

Methods: Anterior tibial arterial wall specimens were obtained from 8 patients with type 2 diabetes mellitus and 8 patients who experienced a traffic accident.

Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells.

CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex.

Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice.

Background And Purpose: Numerous in vitro studies have suggested that digoxin suppresses inflammation and alters lipid metabolism. However, the effect of dioxin on atherosclerosis is poorly understood. The present study was conducted to determine whether digoxin affects the development of atherosclerosis in a murine model of atherosclerotic disease.