Atherosclerosis (AS), with associated risk of stroke or cerebrovascular disease, is one of the most common causes of death globally. It has been well established that tripartite motif‐containing protein 7 Tripartite Motif‐containing 7 (Trim7), as an E3 ubiquitin protein ligase, is involved in protein ubiquitination and thus regulating cellular proliferation. Moreover, TRIM7 is upregulated in advanced carotid AS. However, the detailed mechanism of TRIM7 on regulation of AS remains unclear. In the present study, we firstly discovered that TRIM7 expression was robustly induced in platelet‐derived growth factor type BB‐treated vascular smooth muscle cells (VSMCs) and human atherosclerotic plaques. Functional approaches established that knockdown of TRIM7 inhibited proliferation and migration of VSMCs, as well as arrested the cell cycle at G1‐S, thus suppressing AS progression. Our results also identified that c‐Jun/activator protein 1 (AP‐1) signaling pathway was activated by TRIM7. Moreover, gain‐ and loss‐of‐function studies revealed that TRIM7 could promote proliferation and migration of VSMCs via activation of c‐Jun/AP‐1 signaling pathway. Finally, by using atherogenic apolipoprotein E‐deficient (apoE–/–) C57BL/6 mice with high‐fat diet AS model, we demonstrated that interference of TRIM7 could effectively mitigate in vivo AS via inactivation of c‐Jun/AP‐1 signaling pathway. In general, activation of c‐Jun/AP‐1 signaling pathway via TRIM7 could be an important mechanism in AS progression, thus shedding light on the development of novel therapeutics to the treatment of the disease.

BackgroundA prolonged PR interval is a sign of increased risk of cardiac arrhythmia. Recent genome-wide association studies found that the single-nucleotide polymorphism (SNP) rs3825214 in T-box 5 (TBX5) was positively associated with PR interval, QRS duration, QT interval, and common arrhythmia disorders such as atrial fibrillation (AF) and advanced atrioventricular block. However, other independent replication studies are required to validate the result. This study assessed associations between rs3825214 and ECG parameters, AF, and ventricular tachycardia (VT) in a Chinese Han population.Methodology/Principal FindingsTo assess the association between rs3825214 and AF and VT, we carried out case-control association studies with 692 AF patients (including 275 lone AF patients), 235 VT patients, and 856 controls. Genotyping was performed using a Rotor-Gene TM 6000 High Resolution Melt system. Statistical analyses of associations were adjusted for potential confounding factors. A moderate association was detected between rs3825214 and AF (P adj = 0.036, OR = 0.79) and a highly significant association was detected between the G allele of rs3825214 and lone AF (P adj = 0.001, OR = 0.65; genotypic P = 3.75×10−4 with a dominant model). We also found that rs3825214 showed a significant association with atrial-ventricular block (AVB; P = 0.028; P adj = 0.035, OR = 0.494).ConclusionsOur results indicate that rs3825214 conferred a significant risk of lone AF in this Chinese Han population.

Contemporary studies have identified rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene as a new genetic marker in modulating the QT interval and sudden cardiac death (SCD) in general populations. However, the conclusions were not coincident. Therefore, we conducted for the first time a system evaluation of the relativity of rs10494366, the QT interval, and sudden death by meta-analysis. In our study, the meta-analysis displayed the GG genotype of rs10494366 correlated with the QT interval in women with no heterogeneity, and in diabetes mellitus (DM) patients with minor heterogeneity. In the Caucasian population, the correlation of rs10494366 and sudden death was significant. The heterogeneity referred to the relevance between rs10494366 and sudden death in the Asian population. In conclusion, the minor allele of rs10494366 may have an impact on the QT interval in women or DM patients and may have a potential role in sudden death in the Caucasian population.

Nuclear receptor‐binding SET domain 3 (NSD3) is a lysine methyltransferase that plays important roles in multiple biological activities; however; its potential roles in the cardiovascular system remain unknown. In this study, we found that NSD3 expression is reduced by isoproterenol (ISO) stimuli both in vitro and in vivo. Overexpression of NSD3 attenuates ISO‐induced cardiomyocyte hypertrophy. Mechanistically, ISO treatment decreases H3K27me2/3 modifications on the atrial natriuretic factor (ANF) promoter by suppressing NSD3 and inhibits the association between NSD3 and bromodomain‐containing protein 4 (BRD4), thus suppressing the BRD4‐mediated H3K27ac modifications, which ultimately promote ANF transcription and cardiomyocyte hypertrophy. In conclusion, NSD3 decreases ANF expression and, thereby, attenuates ISO‐induced cardiomyocyte hypertrophy.