Background:The role of miR-1 and miR-133 in regulating the expression of potassium and calcium ion channels, and mediating cardiomyocyte apoptosis in mice with viral myocarditis (VMC) is investigated herein. Methods: Male Balb/c mice were randomly divided into groups: control group, VMC group, VMC + + miR-1/133 mimics group, or VMC + miR-1/133 negative control (NC) group. VMC was induced with coxsackievirus B3 (CVB3). MiR-1/133 mimics ameliorated cardiac dysfunction in VMC mice and was compared to the VMC+NC group. Results: Hematoxylin and eosin staining showed a well-arranged myocardium without inflammatory cell infiltration in the myocardial matrix of the control group. However, in the VMC and VMC+NC groups, the myocardium was disorganized and swollen with necrosis, and the myocardial matrix was infiltrated with inflammatory cells. These changes were alleviated by miR-1/133 mimics. TUNEL staining revealed decreased cardiomyocyte apoptosis in the VMC + miR-1/133 mimics group compared with the VMC group. In addition, miR-1/133 mimics up-regulated the expression of miR-1 and miR-133, the potassium channel genes Kcnd2 and Kcnj2, as well as Bcl-2, and down-regulated the expression of the potassium channel suppressor gene Irx5, L-type calcium channel subunit gene a1c (Cacna1c), Bax, and caspase-9 in the myocardium of VMC mice. MiR-1/133 also up-regulated the protein levels of Kv4.2 and Kir2.1, and down-regulated the expression of CaV1.2 in the myocardium of VMC mice. Conclusions: MiR-1 and miR-133 decreased cardiomyocyte apoptosis by mediating the expression of apoptosis-related genes in the hearts of VMC mice.

Kawasaki disease (KD) is the leading cause of acquired heart disease in pediatric patients in developed countries. Coronary artery aneurysms and myocardial infarction may occur if the disease remains untreated. An estimated 10–20% of KD patients do not respond to intravenous gamma globulin (IVIG), and thus, alternative treatments are currently being investigated. Epoxyeicosatrienoic acids (EETs) are natural anti-inflammatory factors and angiogenic mediators degraded by soluble epoxide hydrolase (sEH). sEH inhibitory factors have been demonstrated to stabilize EET levels, inhibit inflammation and promote vascular repair in vivo . The present study aimed to determine whether an increase in EET levels induced by treatment with the sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) promotes vascular repair in human coronary arterial endothelial cells (HCAECs) and reduces inflammation in a mouse model of KD induced by Lactobacillus casei cell wall extract. The effect of AUDA on vascular repair in HCAECs was assessed by using cell proliferation, migration, adhesion and tube formation assays, and the anti-inflammatory effect of AUDA in the mouse model of KD was determined by detecting the expression of matrix metalloproteinase (MMP)-9, tumor necrosis factor (TNF)-α and interleukin (IL)-1β at the protein level via ELISA. The results demonstrated that AUDA increased the proliferation, migration, adhesion and tube formation ability of HCAECs in a dose-dependent manner. Furthermore, in the mouse model of KD, AUDA reduced the protein expression of MMP-9, IL-1β and TNF-α, indicating that AUDA may alleviate inflammatory reactions in the coronary arteries of KD model mice. The present results also indicate that these effects may be exerted through the peroxisome proliferator activated receptor γ signaling pathway. Taken together, the present study supports the potential utility of AUDA in the treatment of KD.

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The downregulated methylation level at TBX20 promoter may be responsible for the elevated mRNA expression levels in patients with TOF. The abnormal methylation status of the TBX20 promoter may contribute to the pathogenesis of TOF.

Pulmonary arterial hypertension is a progressive and fatal disease. Recent studies suggest that circular RNA (circRNAs/circs) can regulate various biological processes, including cell proliferation. Therefore, it is possible that circRNA may have important roles in pulmonary artery smooth muscle cell proliferation in hypoxic pulmonary hypertension (HPH). The aim of the present study was to determine the role and mechanism of circRNA-glutamate metabotropic receptor 1 (circ-Grm1; mmu_circ_0001907) in pulmonary artery smooth muscle cell (PASMC) proliferation and migration in HPH. High-throughput transcriptome sequencing was used to screen circRNAs and targeted genes involved in HPH. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2-deoxyuridine and wound healing assays were employed to assess cell viability and migration. Reverse transcription-quantitative PCR and western blotting were used to detect target gene expression in different groups. Bioinformatical approaches were used to predict the interaction probabilities of circ-Grm1 and Grm1 with FUS RNA binding protein (FUS). The interactions of circ-Grm1, Grm1 and FUS were evaluated using RNA silencing and RNA immunoprecipitation assays. The results demonstrated that circ-Grm1 was upregulated in hypoxic PASMCs. Further experiments revealed that the knockdown of circ-Grm1 could suppress the proliferation and migration of hypoxic PASMCs. Transcriptome sequencing revealed that Grm1 could be the target gene of circ-Grm1. It was found that circ-Grm1 could competitively bind to FUS and consequently downregulate Grm1. Moreover, Grm1 could inhibit the function of circ-Grm1 by promoting the proliferative and migratory abilities of hypoxic PASMCs. The results also demonstrated that circ-Grm1 influenced the biological functions of PASMCs via the Rap1/ERK pathway by regulating Grm1. Overall, the current results suggested that circ-Grm1 was associated with HPH and promoted the proliferation and migration of PASMCs via suppression of Grm1 expression through FUS.