MicroRNA-181 in cardiovascular disease: Emerging biomarkers and therapeutic targets.

Cardiovascular disease (CVD) is the leading cause of death worldwide. MicroRNAs (MiRNAs) have attracted considerable attention for their roles in several cardiovascular disease states, including both the physiological and pathological processes. In this review, we will briefly describe microRNA-181 (miR-181) transcription and regulation and summarize recent findings on the roles of miR-181 family members as biomarkers or therapeutic targets in different cardiovascular-related conditions, including atherosclerosis, myocardial infarction, hypertension, and heart failure.

Two-sample Mendelian randomization to study the causal association between gut microbiota and atherosclerosis.

Background: According to some recent observational studies, the gut microbiota influences atherosclerosis via the gut microbiota-artery axis. However, the causal role of the gut microbiota in atherosclerosis remains unclear. Therefore, we used a Mendelian randomization (MR) strategy to try to dissect this causative link.

No evidence of coronary plaque stabilization by allopurinol in patients with acute coronary syndrome.

Background: Allopurinol, a xanthine inhibitor that lowers uric acid concentration, has been proven to reduce inflammation and oxidative stress in patients with cardiovascular disease. However, it is unknown whether these beneficial effects translate into favorable plaque modification in acute coronary syndromes (ACS). This study aimed to investigate whether allopurinol could improve coronary plaque stabilization using coronary computed tomography angiography (CCTA).

CircRNA/lncRNA-miRNA-mRNA network and gene landscape in calcific aortic valve disease.

Background: Calcific aortic valve disease (CAVD) is a common valve disease with an increasing incidence, but no effective drugs as of yet. With the development of sequencing technology, non-coding RNAs have been found to play roles in many diseases as well as CAVD, but no circRNA/lncRNA-miRNA-mRNA interaction axis has been established. Moreover, valve interstitial cells (VICs) and valvular endothelial cells (VECs) play important roles in CAVD, and CAVD differed between leaflet phenotypes and genders.

Single-cell landscape dissecting the transcription and heterogeneity of innate lymphoid cells in ischemic heart.

Background: Until now, few articles have revealed the potential roles of innate lymphoid cells (ILCs) in cardiovascular diseases. However, the infiltration of ILC subsets in ischemic myocardium, the roles of ILC subsets in myocardial infarction (MI) and myocardial ischemia-reperfusion injury (MIRI) and the related cellular and molecular mechanisms have not been described with a sufficient level of detail.

Method: In the current study, 8-week-old male C57BL/6J mice were divided into three groups: MI, MIRI and sham group.

Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils.

Development of abdominal aortic aneurysms (AAA) enhances lesion group-2 innate lymphoid cell (ILC2) accumulation and blood IL5. ILC2 deficiency in Rora Il7r mice or induced ILC2 depletion in Icos Cd4 mice expedites AAA growth, increases lesion inflammation, but leads to systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies show that ILC2 protect mice from AAA formation via IL5 and EOS.

Group 2 innate lymphoid cells protect mouse heart from myocardial infarction injury via interleukin 5, eosinophils, and dendritic cells.

Aims: Group 2 innate lymphoid cells (ILC2s) regulate adaptive and innate immunities. In mouse heart, production of myocardial infarction (MI) increased ILC2 accumulation, suggesting a role for ILC2 in cardiac dysfunction post-MI.

Methods And Results: We produced MI in ILC2-deficeint Rorafl/flIl7rCre/+ mice and in Icosfl-DTR-fl/+Cd4Cre/+ mice that allowed diphtheria toxin-induced ILC2 depletion.

Construction and Bioinformatics Analysis of circRNA-miRNA-mRNA Network in Acute Myocardial Infarction.

Acute myocardial infarction (AMI) is one of the main fatal diseases of cardiovascular diseases. Circular RNA (circRNA) is a non-coding RNA (ncRNA), which plays a role in cardiovascular disease as a competitive endogenous RNA (ceRNA). However, their role in AMI has not been fully clarified.

Induction of Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury in Mice.

Acute myocardial infarction is a common cardiovascular disease with high mortality. Myocardial reperfusion injury can counteract the beneficial effects of heart reflow and induce secondary myocardial injury. A simple and reproducible model of myocardial infarction and myocardial ischemia-reperfusion injury is a good tool for researchers.

Innate Lymphoid Cells and Myocardial Infarction.

Myocardial infarction results from obstruction of a coronary artery that causes insufficient blood supply to the myocardium and leads to ischemic necrosis. It is one of the most common diseases threatening human health and is characterized by high morbidity and mortality. Atherosclerosis is the pathological basis of myocardial infarction, and its pathogenesis has not been fully elucidated.

Bortezomib alleviates myocardial ischemia reperfusion injury via enhancing of Nrf2/HO-1 signaling pathway.

Bortezomib is a classical proteasome inhibitor and previous researches have reported its roles of anti-oxidation and anti-inflammatory functions in various diseases. However, the role of Bortezomib in myocardial ischemia reperfusion injury (MIRI) is unclear. Thus, our research seeks to reveal the protective effects of Bortezomib pretreatment in the mice model of MIRI.

Eosinophils improve cardiac function after myocardial infarction.

Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases. Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region. Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes.

Type 2 innate lymphoid cells regulation by regulatory T cells attenuates atherosclerosis.

Regulatory T cells (Tregs) have been shown to attenuate the development and progression of atherosclerosis; however, the exact mechanism is still unclear. In our study, Tregs were adoptively transferred into ApoE mice, and type 2 innate lymphoid cells (ILC2s) were expanded by the IL-2/Jes6-1 complex or depleted by anti-CD90.2 mAb in ApoERag1 mice to study their effects on atherosclerosis.

IL-37 inhibits the maturation of dendritic cells through the IL-1R8-TLR4-NF-κB pathway.

Mature dendritic cells (DCs) play a pathogenic role in atherosclerosis. Our previous study demonstrated that exogenous interleukin (IL)-37 suppresses the maturation of DCs, induces the T-regulatory (Treg) cell response, and attenuates atherosclerosis in ApoE mice. The aim of the present study was to explore the molecular mechanism of IL-37 on the maturation of DCs throughout the development of atherosclerosis.

Growth arrest-specific gene 6 transfer promotes mesenchymal stem cell survival and cardiac repair under hypoxia and ischemia via enhanced autocrine signaling and paracrine action.

Poor cell viability after transplantation has restricted the therapeutic capacity of mesenchymal stem cells (MSCs) for cardiac dysfunction after myocardial infarction (MI). Growth arrest-specific gene 6 (Gas6) encodes a secreted γ-carboxyglutamic acid (Gla)-containing protein that functions in cell growth, adhesion, chemotaxis, mitogenesis and cell survival. In this study, we genetically modified MSCs with Gas6 and evaluated cell survival, cardiac function, and infarct size in a rat model of MI via intramyocardial delivery.

Transgenic Overexpression of IL-37 Protects Against Atherosclerosis and Strengthens Plaque Stability.

Background/aims: Recently, studies have shown that interleukin-37 (IL-37) is involved in atherosclerosis-related diseases. However, the regulatory mechanisms of IL-37 in atherosclerosis remain unknown. This study aims to determine the role of IL-37 in atherosclerosis and to investigate the underlying mechanisms involved.

Sestrin2 Suppresses Classically Activated Macrophages-Mediated Inflammatory Response in Myocardial Infarction through Inhibition of mTORC1 Signaling.

Myocardial infarction (MI) triggers an intense inflammatory response that is essential for dead tissue clearance but also detrimental to cardiac repair. Macrophages are active and critical players in the inflammatory response after MI. Understanding the molecular mechanisms by which macrophage-mediated inflammatory response is regulated is important for designing new therapeutic interventions for MI.

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.

MicroRNA-181b inhibits thrombin-mediated endothelial activation and arterial thrombosis by targeting caspase recruitment domain family member 10.

Thrombogenic and inflammatory mediators, such as thrombin, induce NF-κB-mediated endothelial cell (EC) activation and dysfunction, which contribute to pathogenesis of arterial thrombosis. The role of anti-inflammatory microRNA-181b (miR-181b) on thrombosis remains unknown. Our previous study demonstrated that miR-181b inhibits downstream NF-κB signaling in response to TNF-α.

MicroRNA-181b Improves Glucose Homeostasis and Insulin Sensitivity by Regulating Endothelial Function in White Adipose Tissue.

Rationale: The pathogenesis of insulin resistance involves dysregulated gene expression and function in multiple cell types, including endothelial cells (ECs). Post-transcriptional mechanisms such as microRNA-mediated regulation of gene expression could affect insulin action by modulating EC function.

Objective: To determine whether microRNA-181b (miR-181b) affects the pathogenesis of insulin resistance by regulating EC function in white adipose tissue during obesity.

A Potential Mechanism of High-Dose Ticagrelor in Modulating Platelet Activity and Atherosclerosis Mediated by Thymic Stromal Lymphopoietin Receptor.

Abnormal expression of thymic stromal lymphopoietin (TSLP) and its receptor (TSLPR) was found in patients with acute coronary syndrome. Ticagrelor, an oral platelet ADP P2Y12 receptor antagonist, is widely used in these patients. The aim of this study was to verify whether different doses of ticagrelor regulated plaque progression and platelet activity by modulating TSLP/TSLPR.

mTORC1 signaling is crucial for regulatory T cells to suppress macrophage-mediated inflammatory response after acute myocardial infarction.

Post-infarction inflammatory response results in worse remodeling and dysfunction following myocardial infarction (MI). Supression of post-infarction inflammation would be a logical approach of alleviating post-infarction injury and promoting cardiac repair. In this study, we investigated the significance of mTORC1 signaling in the anti-inflammatory activity of regulatory T cells (Tregs) after MI.

Kruppel-Like Factor 2-Mediated Suppression of MicroRNA-155 Reduces the Proinflammatory Activation of Macrophages.

Objective: Recent evidence indicates that significant interactions exist between Kruppel-like factor 2 (KLF2) and microRNAs (miRNAs) in endothelial cells. Because KLF2 is known to exert anti-inflammatory effects and inhibit the pro-inflammatory activation of monocytes, we sought to identify how inflammation-associated miR-155 is regulated by KLF2 in macrophages.

Approach And Results: Peritoneal macrophages from wild-type (WT) C57Bl/6 mice were transfected with either recombinant adenovirus vector expressing KLF2 (Ad-KLF2) or siRNA targeting KLF2 (KLF2-siRNA) for 24 h-48 h, then stimulated with oxidized low-density lipoproteins (ox-LDL, 50 μg/mL) for 24 h.

Inflammatory cytokine TSLP stimulates platelet secretion and potentiates platelet aggregation via a TSLPR-dependent PI3K/Akt signaling pathway.

Aims: Thymic stromal lymphopoietin (TSLP) plays an important role in inflammatory diseases and is over-expressed in human atherosclerotic artery specimens. The present study investigated the role of TSLP in platelet activation and thrombosis models in vitro and in vivo, as well as the underlying mechanism and signaling pathway.

Methods And Results: Western blotting and flow cytometry demonstrated that the TSLP receptor was expressed on murine platelets.

TSLPR deficiency attenuates atherosclerotic lesion development associated with the inhibition of TH17 cells and the promotion of regulator T cells in ApoE-deficient mice.

Aims: We generated thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice to directly explore the role of thymic stromal lymphopoietin (TSLP) in atherogenesis.

Methods And Results: Both thymic stromal lymphopoietin (TSLP) and its receptor are expressed in atherosclerotic aortas of apolipoprotein E knockout (ApoE KO) mice. Serum thymic stromal lymphopoietin (TSLP) is markedly increased in apolipoprotein E knockout (ApoE KO) mice fed with a high fat diet (HFD).