Angiotensin II (AngII) serves an important inflammatory role in cardiovascular disease; it can induce macrophages to differentiate into the M1‑type, produce inflammatory cytokines and resist pathogen invasion, and can cause a certain degree of damage to the body. Previous studies have reported that connexin 43 (Cx43) and NF‑κB (p65) are involved in the AngII‑induced inflammatory pathways of macrophages; however, the mechanisms underlying the effects of Cx43 and NF‑κB (p65) on AngII‑induced macrophage polarization have not been determined. Thus, the present study aimed to investigate the effects of Cx43 and NF‑κB (p65) on the polarization process of AngII‑induced macrophages. The macrophage polarization‑related proteins and mRNAs were examined by flow cytometry, western blotting, immunofluorescence, ELISA and reverse transcription‑quantitative PCR analyses. RAW264.7 macrophages were treated with AngII to simulate chronic inflammation and it was subsequently found that AngII promoted RAW 264.7 macrophage polarization towards the M1‑type by such effects as the release of inducible nitric oxide synthase (iNOS), tumour necrosis factor (TNF)‑α, IL‑1β, the secretion of IL‑6, and the expression of M1‑type indicators, such as CD86. Simultaneously, compared with the control group, the protein expression levels of Cx43 and phosphorylated (p)‑p65 were significantly increased following AngII treatment. The M1‑related phenotypic indicators, iNOS, TNF‑α, IL‑1β, IL‑6 and CD86, were inhibited by the NF‑κB (p65) signalling pathway inhibitor BAY117082. Similarly, the Cx43 inhibitors, Gap26 and Gap19, also inhibited the expression of M1‑related factors, and the protein expression levels of p‑p65 in the Gap26/Gap19 groups were significantly decreased compared with the AngII group. Altogether, these findings suggested that AngII may induce the polarization of RAW264.7 macrophages to the M1‑type through the Cx43/NF‑κB (p65) signalling pathway.

目的 分析高龄老年心房颤动(AF)患者抗凝治疗情况.方法 收集2016年6月至2018年9月在石河子大学医学院第一附属医院住院高龄老年(≥80岁)AF患者的病史资料,共入选AF患者621例.随访期间,了解抗凝药物使用情况和凝血监测等临床信息,并进行统计分析.结果 根据CHA2D2S-VASc评分法、ATRIA评分法和HAS-BLED评分系统、ORBIT出血风险评分表,621例入组的高龄老年AF患者卒中风险分值较高,但出血风险分值较低.所有入组患者中有25.60％的患者使用华法林抗凝,10.14％的患者使用新型口服抗凝药物,32.37％的患者选择抗血小板治疗,余31.88％的患者未接受任何抗栓治疗.服用抗栓药物的研究对象比未服用者血栓栓塞率更低,而出血率更高,差异有统计学意义.随访成功445例,出院后继续口服抗凝药物为104例(16.75％),定期监测凝血68例(10.95％),发生出血事件51例(8.21％),死亡159例(35.73％).全因死亡组的年龄、收缩压(SBP)、肌酐(Cr)、血栓栓塞、痴呆、合并糖尿病等慢性病、既往吸烟史显著高于对照组,差异有统计学意义.全因死亡组的国际标准化比率(INR)、出血事件、口服抗栓药物明显低于对照组,差异有统计学意义.结论 高龄老年心房颤动患者出院坚持服用抗凝药物的比例较低,定期监测凝血比例较低.并且全因死亡的心房颤动患者服用抗凝药物比例较低.

Cardiac fibroblast (CF) differentiation into myofibroblasts is a crucial cause of cardiac fibrosis, which increases in the extracellular matrix (ECM) stiffness. The increased stiffness further promotes CF differentiation and fibrosis. However, the molecular mechanism is still unclear. We used bioinformatics analysis to find new candidates that regulate the genes involved in stiffness-induced CF differentiation, and found that there were binding sites for the POU-domain transcription factor, POU2F1 (also known as Oct-1), in the promoters of 50 differentially expressed genes (DEGs) in CFs on the stiffer substrate. Immunofluorescent staining and Western blotting revealed that pathological stiffness upregulated POU2F1 expression and increased CF differentiation on polyacrylamide hydrogel substrates and in mouse myocardial infarction tissue. A chromatin immunoprecipitation assay showed that POU2F1 bound to the promoters of fibrosis repressors IL1R2, CD69, and TGIF2. The expression of these fibrosis repressors was inhibited on pathological substrate stiffness. Knockdown of POU2F1 upregulated these repressors and attenuated CF differentiation on pathological substrate stiffness (35 kPa). Whereas, overexpression of POU2F1 downregulated these repressors and enhanced CF differentiation. In conclusion, pathological stiffness upregulates the transcription factor POU2F1 to promote CF differentiation by inhibiting fibrosis repressors. Our work elucidated the crosstalk between CF differentiation and the ECM and provided a potential target for cardiac fibrosis treatment.

目的 观察与心力衰竭相关的不同病理因素刺激下,Sprague-Dawley(SD)乳鼠心肌细胞和心脏成纤维细胞中β3-肾上腺素受体(β3-AR)表达变化的差异.方法 分离培养SD乳鼠心肌细胞和心脏成纤维细胞并行免疫荧光鉴定,分别给予血管紧张素Ⅱ(AngⅡ)及去甲肾上腺素(NE)进行刺激,采用实时荧光定量PCR(qPCR)检测心肌细胞肥大相关基因[心钠肽(ANP)、脑钠肽(BNP)、β-肌球蛋白重链(β-MHC)]、心脏成纤维细胞纤维化相关基因[Ⅰ型胶原蛋白(COL-Ⅰ)、Ⅲ型胶原蛋白(COL-Ⅲ)]及2种细胞中β3-AR的mRNA表达.结果 免疫荧光鉴定显示,分离培养的心肌细胞和心脏成纤维细胞均状态良好.AngⅡ和NE分别刺激2种细胞48 h后,心肌细胞中ANP、BNP、β-MHC和β3-AR的表达较对照组明显增加;心脏成纤维细胞中COL-Ⅰ、COL-Ⅲ表达较对照组明显增加,但β3-AR的表达没有明显变化.结论 参与心力衰竭发生发展的病理因素AngⅡ和NE主要引起心肌细胞的β3-AR表达增加,而不是心脏成纤维细胞.

Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries, which are mainly mediated by β-adrenergic receptors (β-ARs). However, α 1 -adrenergic receptors (α 1 -ARs) are also expressed in the heart and are activated upon acute sympathetic stress. In the present study, we investigated whether α 1 -AR activation induced cardiac inflammation and the underlying mechanisms. Male C57BL/6 mice were injected with a single dose of α 1 -AR agonist phenylephrine (PE, 5 or 10 mg/kg, s.c.) with or without pretreatment with α-AR antagonist prazosin (5 mg/kg, s.c.). PE injection caused cardiac dysfunction and cardiac inflammation, evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5, as well as macrophage infiltration in myocardium. These effects were blocked by prazosin pretreatment. Furthermore, PE injection significantly increased the expression of NOD-like receptor protein 3 (NLRP3) and the cleavage of caspase-1 (p20) and interleukin-18 in the heart; similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE (10 μM). Moreover, PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3 -/- mice compared with wild-type mice. In conclusion, α 1 -AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes.

In heart failure, the expression of cardiac β3-adrenergic receptors (β3-ARs) increases. However, the precise role of β3-AR signaling within cardiomyocytes remains unclear. Transforming growth factor β1 (TGFβ1) is a crucial cytokine mediating the cardiac remodeling that plays a causal role in the progression of heart failure. Here, we set out to determine the effect of β3-AR activation on TGFβ1 expression in rat cardiomyocytes and examine the underlying mechanism. The selective β3-AR agonist BRL37344 induced an increase in TGFβ1 expression and the phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun in β3-AR-overexpressing cardiomyocytes. Those effects of BRL37344 were suppressed by a β3-AR antagonist. Moreover, the inhibition of JNK and c-Jun activity by a JNK inhibitor and c-Jun siRNA blocked the increase in TGFβ1 expression upon β3-AR activation. A protein kinase G (PKG) inhibitor also attenuated β3-AR-agonist-induced TGFβ1 expression and the phosphorylation of JNK and c-Jun. In conclusion, the β3-AR activation in cardiomyocytes increases the expression of TGFβ1 via the PKG/JNK/c-Jun pathway. These results help us further understand the role of β3-AR signaling in heart failure.

Background: The prevalence of atrial fibrillation (AF) increases with age and is associated with high morbidity and mortality. The main objective of this study is to describe the clinical characteristics and antithrombotic status and the factors that determine antithrombotic use in hospitalized elderly patients with AF. Methods: Data were collected involving patients hospitalized at the First Affiliated Hospital of Shihezi Medical University from June 2015 to September 2017. Results: A total of 621 patients with an average age of 82.4 ± 5.0 years (42.3% females; 91.8% Han) were included. The prevalence of risk factors and cardiovascular disease: hypertension (56.5%), heart failure (38.2%), coronary artery disease (76.8%), and carotid atherosclerosis (21.3%). Among the 621 patients, 35.7% were taking oral anticoagulant therapy (OAT) including warfarin (25.6%) or a novel oral anticoagulant (10.1%), 32.4% of patients were taking oral antiplatelet therapy, and 31.9% received 17 anticoagulant therapy. According to the European Guidelines for AF management, CHA2DS2-VASc score was used for stroke risk stratification. All patients in this study had a score of ≥2; However, the rate of OAT was 35.7%. Follow-up data were available for 97.3% of the patients (n = 604), of which 26.6% of patients (n = 159) were deceased and 16.75% of patients (n = 104) continued to receive anticoagulation treatment. Hospitalized patients older than 80 years with AF showed numerous comorbidities. The percentage of appropriately anticoagulated patients was suboptimal according to CHA2DS2-VASc score, with only 35.7% of those requiring treatment receiving it. Conclusion: The percentage of patients with AF appropriately anticoagulated at the First Affiliated Hospital of Shihezi Medical University is at a substandard level.