Macrophage is a vital factor in determining the fate of abdominal aortic aneurysm (AAA). The crosstalk between macrophage and other cells plays a crucial role in the development of aneurysm. Gasdermin D (GSDMD) is a vital executive protein of pyroptosis, which is a novel programmed cell death associated with inflammation. In this study, we identified aortic macrophage as the main expressing cell of GSDMD in AAA. Using Gsdmd-/-ApoE-/- mouse and AAV-F4/80-shGSDMD, we demonstrated the potential role of macrophage-derived GSDMD in AAA and aortic pyroptosis induced by Ang II in vivo. In vitro experiments showed that GSDMD promotes the pyroptosis of mouse primary peritoneal macrophages (MPMs), murine aortic vascular smooth muscle cells (MOVAS) and primary smooth muscle cells. Mechanistically, a mouse cytokine antibody array showed that Gsdmd-/- inhibited LPS + nigericin (LN)- induced secretion of multiple cytokines from MPMs. Furthermore, GSDMD is involved in the crosstalk between MPMs and MOVAS via cytokine secretion. This study provides a novel fundamental insight into macrophage-derived GSDMD in AAA and showed that GSDMD could be a promising therapeutic target for AAA.

TIMP metallopeptidase inhibitor 3 (TIMP-3) may contribute to the pathogenesis of venous thromboembolism (VTE). However, few studies have investigated the effect of TIMP-3 on VTE. Therefore, a two-sample Mendelian randomization (MR) analysis was conducted to investigate the association between TIMP-3 levels and VTE. Seven independent single-nucleotide polymorphisms (SNPs) for TIMP-3 levels were obtained from a published genome-wide association study (the KORA Consortium, including 997 Europeans). We obtained outcome datasets for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen Consortium. The primary analytical method used in the MR analysis was the inverse variance weighted (IVW) method. To enhance the robustness of the MR results, some other MR methods including weighted median, MR-Egger, and MR-PRESSO were conducted. Moreover, several sensitivity analyses were performed to identify potential horizontal pleiotropy and heterogeneity. In primary IVW MR analyses, per log increase in genetically predicted TIMP-3 levels were positively associated with the incidence of VTE (odds ratio [OR], 1.03; 95% confidence interval (CI), 1.01, 1.06; P = 0.010), PE (OR, 1.04; 95% CI, 1.01, 1.08; P = 0.009), and DVT (OR, 1.06; 95% CI, 1.02, 1.10; P= 0.003). The results of the weighted median, MR-Egger, and MR-PRESSO were similar to the main findings. No unbalanced pleiotropy or heterogeneity was observed. The study suggests that genetically predicted high levels of TIMP-3 may be associated with an increased risk of VTE. These findings indicate that strategies targeting TIMP-3 may provide a basis for the prevention and treatment of VTE. Further investigation is required to clarify this potential mechanism.

Aim: Hypertensive nephropathy is a common complication of hypertension. However, no effective measures are currently available to prevent the progression of renal insufficiency. Gasdermin D (GSDMD) is a crucial mediator of pyroptosis that induces an excessive inflammatory response. In the present study, we aimed to determine the effect of GSDMD on the pathogenesis of hypertensive nephropathy, which may provide new insights into the treatment of hypertensive nephropathy. Methods: C57BL/6 (wild-type, WT) and Gsdmd knockout (Gsdmd(-/-)) mice were subcutaneously infused with angiotensin II (Ang II) via osmotic mini-pumps to establish a hypertensive renal injury model. Recombinant adeno-associated virus serotype 9 (AAV9) carrying GSDMD cDNA was used to overexpress GSDMD. Renal function biomarkers, histopathological changes, and inflammation and fibrosis indices were assessed. Transcriptome sequencing (RNA-seq) and cleavage under targets and mentation (CUT & Tag) experiments were performed to identify the downstream pathogenic mechanisms of GSDMD in hypertensive nephropathy. Results: GSDMD was activated in the kidneys of mice induced by Ang II (P < 0.001). This activation was primarily observed in the renal tubular epithelial cells (P < 0.0001). GSDMD deficiency attenuated renal injury and fibrosis induced by Ang II (P < 0.0001), whereas Gsdmd overexpression promoted renal injury and fibrosis (P < 0.01). Mechanistically, GSDMD increased Ang II-induced GATA binding protein 2 (GATA2) transcription factor expression (P < 0.01). GATA2 also bound to the aquaporin 4 (Aqp4) promoter sequence and facilitated Aqp4 transcription (P < 0.001), leading to renal injury and fibrosis. Moreover, treatment with GI-Y1, an inhibitor of GSDMD, alleviated Ang II-induced renal injury and fibrosis (P < 0.01). Conclusion: GSDMD plays an important role in the development of hypertensive nephropathy. Targeting GSDMD may be a therapeutic strategy for the treatment of hypertensive nephropathy.

Vascular smooth muscle cells (VSMCs) are primarily responsible for vasoconstriction and the regulation of blood pressure1. Pyroptosis, a particular form of regulated cell death, is involved in multiple vascular injuries, including hypertensive vascular dysfunction. This pyroptotic cell death is mediated by the pore-forming protein of Gasdermin D (GSDMD). This study was designed to examine the direct effect of GSDMD on smooth muscle cell pyroptosis and vascular remodeling. Findings revealed that GSDMD was activated in Angiotensin (Ang) II- treated aortas. We then showed that genetic deletion of Gsdmd reduced vascular remodeling and aorta pyroptosis induced by Ang II in vivo. Aberrant expression of GSDMD by recombinant AAV9 virus carrying Gsdmd cDNA aggravated the level of pyroptosis in aortas of Ang II mice. Gain- and loss-of- function analysis further confirmed that GSDMD regulated the pyroptosis of murine aortic vascular smooth muscle cells (MOVAS) in an in vitro model of tumor necrosis factor (TNF)-α treatment, which was achieved by transfecting expressing plasmid or siRNA, respectively. Overall, this study provided evidence supporting the active involvement of GSDMD in smooth muscle cell pyroptosis and Ang II-induced mice vascular injury. This finding lends credence to GSDMD as a potential therapeutic target for hypertensive vascular remodeling via inhibiting pyroptosis.

Cardiac hypertrophy leads to myocardial dysfunction and represents a serious threat to global public health security. Deubiquitinating enzymes (DUBs) mainly maintain the stability of substrate proteins and are essential to cardiac pathophysiology. Here, we explored the role and regulating mechanism of a DUB, Josephin domain-containing protein 2 (JOSD2), in cardiac hypertrophy. We found that JOSD2 expression was significantly upregulated in hypertrophic myocardium. Josd2 gene knockout aggravated cardiac dysfunction and hypertrophy in mice, whereas cardiac overexpression of JOSD2 mediated by the AAV9 vector prevented angiotensin II-induced cardiac hypertrophy. A comprehensive proteome-wide quantitative analysis identified sarco/endoplasmic reticulum calcium ATPase 2a (SERCA2a) as a key substrate of JOSD2. Mechanistically, JOSD2 mediates SERCA2a deubiquitination, enhancing the stability of SERCA2a. By regulating SERCA2a, JOSD2 deficiency impairs calcium handling and promotes hypertrophy in primary cardiomyocytes. Our findings highlight the promise of JOSD2 as a beneficial therapeutic target for hypertrophic cardiomyopathy and provide an additional strategy for SERCA2a-targeted therapy.

Associations between ultrafine particles (UFPs) and hourly onset of acute myocardial infarction (AMI) have rarely been investigated. We aimed to evaluate the impacts of UFPs on AMI onset and the lag patterns. A time-stratified case-crossover study was performed among 20,867 AMI patients from 46 hospitals in Shanghai, China, between January 2015 and December 2020. Hourly data of AMI onset and number concentrations of nanoparticles of multiple size ranges below 0.10 μm (0.01-0.10, UFP/PNC0.01-0.10; 0.01-0.03, PNC0.01-0.03; 0.03-0.05, PNC0.03-0.05; and 0.05-0.10 μm, PNC0.05-0.10) were collected. Conditional logistic regressions were applied. Transient exposures to these nanoparticles were significantly associated with AMI onset, with almost linear exposure-response curves. These associations occurred immediately after exposure, lasted for approximately 6 h, and attenuated to be null thereafter. Each interquartile range increase in concentrations of total UFPs, PNC0.01-0.03, PNC0.03-0.05, and PNC0.05-0.10 during the preceding 0-6 h was associated with increments of 3.29, 2.08, 2.47, and 2.93% in AMI onset risk, respectively. The associations were stronger during warm season and at high temperatures and were robust after adjusting for criteria air pollutants. Our findings provide novel evidence that hourly UFP exposure is associated with immediate increase in AMI onset risk.

Doxorubicin (Dox), as a widely used anthracycline antitumor drug, can cause severe cardiotoxicity. Cardiomyocyte death and inflammation are involved in the pathophysiology of Dox-induced cardiotoxicity (DIC). Gasdermin D (GSDMD) is known as a key executioner of pyroptosis, which is a pro-inflammatory programmed cell death. We aimed to investigate the impact of GSDMD on DIC and systematically reveal its underlying mechanisms. Our findings indicated that Dox induced cardiomyocyte pyroptosis in a GSDMD-dependent manner by utilizing siRNA or overexpression-plasmid technique. We then generated GSDMD global knockout mice via CRISPR/Cas9 system and found that GSDMD deficiency reduced Dox-induced cardiomyopathy. Dox induced the activation of inflammatory caspases, which subsequently mediated GSDMD-N generation indirectly. Using molecular dynamics simulation and cell-free systems, we confirmed that Dox directly bound to GSDMD and facilitated GSDMD-N-mediated pyroptosis. Furthermore, GSDMD also mediated Dox-induced mitochondrial damage via Bnip3 and mitochondrial perforation in cardiomyocytes. These findings provide fresh insights into the mechanism of how Dox-engaged GSDMD orchestrates adverse cardiotoxicity and highlight the prospects of GSDMD as a potential target for DIC.

Background: Cardiac hypertrophy is initially an adaptive response of cardiomyocytes to neurohumoral or hemodynamic stimuli. Evidence indicates that Ang II (angiotensin II) or pressure overload causes GSDMD (gasdermin D) activation in cardiomyocytes and myocardial tissues. However, the direct impact of GSDMD on cardiac hypertrophy and its underlying mechanisms are not fully understood. Methods and Results: In this study, we examined the aberrant activation of GSDMD in mouse and human hypertrophic myocardia, and the results showed that GSDMD deficiency reduced Ang II or pressure overload-induced cardiac hypertrophy, dysfunction, and associated cardiomyocyte pyroptosis in mice. Mechanistically, Ang II-mediated GSDMD cleavage caused mitochondrial dysfunction upstream of STING (stimulator of interferon genes) activation in vivo and in vitro. Activation of STING, in turn, potentiated GSDMD-mediated cardiac hypertrophy. Moreover, deficiency of both GSDMD and STING suppressed cardiac hypertrophy in cardiac-specific GSDMD-overexpressing mice. Conclusions: Based on these findings, we propose a mechanism by which GSDMD generates a self-amplifying, positive feed-forward loop with the mitochondria-STING axis. This finding points to the prospects of GSDMD as a key therapeutic target for hypertrophy-associated heart diseases.

Atherosclerosis is the common pathophysiological foundation of ischaemic stroke and myocardial ischaemia. Oxidative stress is intricately related to the progress of atherosclerosis. DL-3-n-butylphthalide (NBP) is a synthesized raceme of L-3-n-butylphthalide that is first isolated from celery. As a neuroprotective agent, NBP also exhibits potent antioxidative activity. Our research aimed to evaluate the effect of NBP on atherosclerosis and to explore the underlying antioxidative mechanisms and targets. Firstly, we detected the protective effect of NBP on ApoE-/- model of atherosclerosis. NBP showed high efficiency as a therapeutic agent against the formation of atherosclerotic plaques and oxidative events in HFD-treated ApoE-/- mice. We have also evaluated the effect of NBP on oxidized-LDL (oxLDL)-induced oxidative damage and Keap-1/ Nrf-2 interaction by utilizing rat aortic endothelial cells (ECs) and mouse primary peritoneal macrophages (MPMs). Furthermore, we investigated the possibility that NBP improves oxLDL-stimulated oxidative stress in a Keap-1- dependent way in ECs by siRNA technique. Using molecular dynamics (MD) simulation, we detected that Keap-1, a negative adaptor of Nrf-2, may be one of the target protein of NBP. Our studies show that amelioration of oxidative stress by NBP may provide a potential therapeutic strategy for atherosclerosis or cardio-cerebrovascular events from atherosclerosis.

信息化时代的来临致使各行各业的发展模式需要变更,因为传统的医院管理模式已经不适应信息化背景的发展势态.联合信息技术创新医院管理模式是必然之举,毕竟国家一直以来十分重视医疗卫生事业的发展.医院若想要达到良性发展目标,则需要灵活应用现代信息技术革新管理模式.目前,传统的管理制度已无法支持现代医学事业的正常发展,某种程度上已变成其发展的阻碍.信息化管理模式不但能提高医院管理规模化,还能有效缓解医患矛盾.基于此,文章从医院管理模式发展概述展开分析,探究了信息化新形势下医院管理模式存在的问题,提出建设性改进措施以供参考.

目的 探讨基于专科医联体的标准版-基层版胸痛中心体系与普通区域救治体系对急性ST段抬高型心肌梗死(STEMI)患者救治效果的影响.方法 嘉兴学院附属第二医院通过国家胸痛中心(标准版)认证之后,与其中一家网络医院建立心血管专科医联体,并帮扶其建设基层版胸痛中心,成立标准版-基层版胸痛中心体系.回顾该体系(2017年2月至2019年12月)转运经皮冠状动脉介入治疗(PCI)的STEMI患者作为观察组(40例),回顾同时段的其他10余家网络医院转运PCI的STEMI患者为对照组(121例).对比两组患者总缺血时间、首次医疗接触(FMC)时间、网络医院入门至转出(DIDO)时间、FMC-导丝通过(FMC-to-W)时间、大门-导丝通过(D-to-W)时间及达标率,绕行急诊比例,院内心力衰竭、死亡率,住院天数及费用.结果 观察组DIDO时间[(52.35±46.07)min比(77.15±76.75)min,P=0.015]、D-to-W时间[(60.98±27.31)min比(71.35±24.65)min,P=0.026]均短于对照组,但途中转运时间[(52.45±6.08)min比(41.56±11.37)min,P=0.001]长于对照组,差异均有统计学意义.两组患者FMC-to-W时间、住院天数、住院费用比较,差异均无统计学意义(均P>0.05).观察组患者的绕行急诊比例(40.0％比11.6％,P<0.001)、DIDO 30 min达标率(37.5％比11.6％,P<0.001)均高于对照组,差异均有统计学意义.两组患者院内90 min再灌注率、FMC-to-W 120 min达标率、院内心力衰竭发生率和死亡率比较,差异均无统计学意义(均P>0.05).结论 基于专科医联体的标准版-基层版胸痛中心体系,能够提高心肌梗死的区域协同救治能力和运行效果,且质量优于普通的胸痛中心救治体系.

Pressure overload leads to a hypertrophic milieu that produces deleterious cardiac dysfunction. Inflammation is a key pathophysiological mechanism underpinning myocardial hypertrophy. DL-3-n-butylphthalide (NBP), a neuroprotective agent, also has potent cardioprotective effects. In this study, the potential of NBP to antagonize myocardial hypertrophy was evaluated in C57BL/6 mice in vivo and in rat primary cardiomyocytes in vitro. In mice, NBP treatment reduced cardiac hypertrophy and dysfunction in a transverse aortic constriction (TAC)-induced pressure overload model. In angiotensin (Ang) II-challenged cardiomyocytes, NBP prevents cell size increases and inhibits gasdermin D (GSDMD)-mediated inflammation. Furthermore, overexpression of GSDMD-N reduced the protective effects of NBP against Ang II-induced changes. Using molecular docking and MD simulation, we found that the GSDMD-N protein may be a target of NBP. Our study shows that NBP attenuates myocardial hypertrophy by targeting GSDMD and inhibiting GSDMD-mediated inflammation.

Cardiac hypertrophy is a current, major, global health challenge. Oxidative stress is an important mechanism that contributes to the pathogenesis of cardiac hypertrophy. Schisandra chinensis polysaccharides (SCP), the primary active constituent in Schisandra chinensis, have antioxidative properties. Here, we investigated the role played by SCP in a cardiac hypertrophy model mouse induced by transverse aortic constriction (TAC). We found that SCP treatment improved cardiac function by inhibiting myocardial hypertrophy and oxidative stress. Angiotensin II was used to induce cardiomyocyte hypertrophy and oxidative stress in vitro. We discovered that the antioxidant effects of SCP were mediated through the regulation of the thioredoxin-interacting protein (TXNIP)/Thioredoxin-1 (Trx-1) pathway. Using molecular docking, we found that SCP binds to Arg207, Ser169, Lys166, Lys286 and Ser285 in TXNIP through hydrogen bonds. TXNIP is an endogenous inhibitor of Trx-1, and the binding SCP with TXNIP may restrict or interfere with the binding between TXNIP and Trx-1, resulting in Trx-1 activation. In conclusion, our findings demonstrated that the potential use of SCP as a TXNIP inhibitor to attenuate oxidative stress, suggesting that TXNIP might represent a potential therapeutic target for the treatment of cardiac hypertrophy.

This work aimed to study the diagnostic value of dynamic electrocardiogram (ECG) based on P wave detection algorithm for arrhythmia after hepatectomy in patients with primary liver cancer, and to compare the therapeutic effect of different doses of Betaloc. P wave detection algorithm was introduced for ECG automatic detection and analysis, which can be used for early diagnosis of arrhythmia. Sixty patients with arrhythmia after hepatectomy for primary liver cancer were selected as the research objects. They were randomly divided into control group, SD group, MD group, and HD group, with 15 cases in each group. No Betaloc, low-dose (≤47.5 mg), medium-dose (47.5–95 mg), and high-dose (142.5–190 mg) Betaloc were used for treatment. As a result, P wave detection algorithms can mark P waves that may be submerged in strong interference. P waves from arrhythmia database were used to verify the performance of the proposed algorithm. The prediction precision (Pp) of ventricular arrhythmia and atrial arrhythmia was 98.53% and 98.76%, respectively. Systolic blood pressure (117.35 ± 7.33, 126.44 ± 9.38, and 116.02 ± 8.2) mmHg in SD group, MD group, and HD group was significantly lower than that in control group (140.3 ± 7.21) mmHg after two weeks of treatment. Moreover, those of SD group and HD group were significantly lower than MD group (P<0.05). The effective rate of cardiac function improvement in SD group (72.35 ± 1.21%) was significantly higher than that in control group, MD group, and HD group (38.2 ± 0.98%, 65.12 ± 1.33%, and 60.43 ± 1.25%; P<0.05). In short, dynamic ECG based on P wave detection algorithm had high diagnostic value for arrhythmia after hepatectomy in patients with primary liver cancer. It was safe and effective for patients to choose small dose of Betaloc.

Background. Cardiac hypertrophy is one of the initial disorders of the cardiovascular system and can induce heart failure. Oxidative stress is an important pathophysiological mechanism of cardiac hypertrophy. Wogonin (Wog), an important flavonoid derived from the root of Scutellaria baicalensis Georgi, is known to possess antioxidant properties. Methods. An in vitro model of cardiac hypertrophy was established by stimulating H9C2 cells and neonatal rat cardiomyocytes (NRCMs) with angiotensin II (AngII). The indices related to myocardial hypertrophy and oxidative stress were detected. An in vivo model of cardiac hypertrophy was induced by transverse aortic constriction (TAC) in C57BL/6 mice. Cardiac function was monitored by chest echocardiography, and the hypertrophy index was measured. The mice were then sacrificed for histological assays, with mRNA and protein detection. To further explore the role of nuclear factor- (erythroid-derived 2-) like 2 (Nrf-2) in regulating the antioxidant effects of Wog in cardiac hypertrophy, siRNA analysis was conducted. Results. Our results showed that Wog significantly ameliorated AngII-induced cardiomyocyte hypertrophy by inhibiting oxidative stress in H9C2 cells and NRCMs. In addition, Wog treatment prevented oxidative stress and improved cardiac hypertrophy in mice that underwent TAC. Using gene-specific siRNA for Nrf-2, we discovered that these antioxidative effects of Wog are mediated through Nrf-2 induction. Conclusions. Our results provide further evidence for the potential use of Wog as an antioxidative agent for treatment of cardiac hypertrophy, and Nrf-2 might serve as a therapeutic target in the treatment of cardiac hypertrophy.

Abstract Background The incidence of in-stent restenosis (ISR) in patients with diabetes mellitus (DM) after percutaneous coronary intervention (PCI) is significantly higher than that in patients without DM, but the mechanism is not clear. We hypothesised that patients with and risk factors including dyslipidaemia, elevated inflammatory factors would be prone to induction of ISR, and that dynamic observation of the comprehensive risk factor changes before and after PCI would be helpful to identify ISR . Methods This prospective cohort study consecutively enrolled 360 patients who received coronary drug-eluting stent implantation. Patients who underwent coronary angiography (CAG) and received clinical follow-up were prospectively reviewed. The patients were assigned to a DM (262) or a non-DM (98) group. The patients were further assigned according to whether ISR was present to the non-DM + non-ISR, non-DM + ISR, DM + non-ISR, and DM + ISR groups. The patients were further assigned according to whether low-density lipoprotein (LDL-c) was decreased more than 50% compared with baseline, or was less than 1.80 mmol/L in the follow-up, to the LDL-c achieved or the LDL-c failure groups. Results DM patients were prone to develop ISR after PCI and the degree of coronary stenosis was more severe than in non-DM patients. This result was more striking in DM and LDL-c failure patients. The levels of total cholesterol (TC), triglyceride, high-density lipoprotein (HDL-c), LDL-c, apolipoprotein B100, apolipoprotein E, remnant lipoprotein, TC/HDL-c ratio and triglyceride/HDL-c ratio in the DM + non-ISR were similar to those in the DM + ISR group before PCI and CAG. .The DM + ISR group had the highest levels of haemoglobin A1c and the highest Gensini scores. The inflammatory index changes including leukocytes and neutrophils were the most striking in the DM + ISR group. In multivariate regression analysis, neutrophil changes and glycosylated haemoglobin were independent risk factors for ISR [△neutrophil, OR 1.929,95% CI 1.216–3.058; HbA1-c OR 1.559,95% CI 1.001–1.707]. Conclusion Coronary artery disease patients with DM had a high risk for ISR if they had preoperative risk factors including dyslipidaemia, elevated inflammatory factors, and a high Gensini score. Dynamic observation of the changes of the preoperative and postoperative comprehensive risk factors was helpful to identify ISR in patients with DM.

目的 探讨中国胸痛中心(CPC)建设过程中医院行政特点及其他因素的作用.方法 纳入2014年4月至2017年9月通过中国CPC认证的276家医院,根据认证时间分为阶段1(2014年至2015年)和阶段2(2016年至2017年),根据医院院长/副院长的专业是否含有心血管内科学分为A组(心血管内科学专业)141家和B组(非心血管内科学专业)135家,分析比较两组单位在认证类型、认证批次、认证时间、医院等级、医院性质、时间阶段等方面的情况.结果 A组单位标准版(87.2％比70.4％,P=0.001)、三级医院(84.4％比71.1％,P=0.009)、阶段1(24.8％比13.3％,P=0.021)、地区首批CPC(16.3％比8.1％,P=0.045)比例均高于B组单位;而基层版(12.8％比29.6％,P=0.001)、二级医院(15.6％比28.9％,P=0.009)、直辖市(8.5％比19.3％,P=0.010)、阶段2(75.2％比86.7％,P=0.021)、非地区首批CPC(83.7％比91.9％,P=0.045)比例均低于B组单位,差异均有统计学意义.结论 医院行政管理在CPC的建设中发挥重要作用,有心血管内科学专业的医院行政人员更加重视及有利于CPC建设.卫生行政管理部门对CPC建设的推动作用正在显现.

MicroRNAs (miRs) have been demonstrated to regulate physiological and pathological processes. Numerous miRsprotect against cardiomyocyte injury induced by oxidative stress. However, the function of miR-190 still remains unclear. Here, we determined the expression level of miR-190 in H9c2 cells under H2O2 treatment and found that miR-190 expression was significantly inhibited by H2O2. Further study indicated that miR-190 significantly reduced cell apoptosisand the LDH and MDA levels of H9c2 cells induced by H2O2. Luciferase activity assay, quantitative real-time-PCR, and Western blot demonstrated that miR-190 directly targets MAPK8. Rescue experiment confirmed this hypothesis. Further study has revealed that miR-190 protects H9c2 cells from oxidative stress injury through inhibiting the MAPK8/ERK signal pathway. In conclusion, these data suggest that miR-190 protects against oxidative stress injury of H9c2 cells induced by H2O2 through inhibiting MAPK8 expression and the MAPK8/ERK pathway. Our findings provide a potential therapeutic target to promote functional recovery after cardiac ischemia/reperfusion.

急性冠状动脉综合征(acute coronary syndromes,ACS)是临床危重症疾病之一,并发症多,死亡率高[1].HCS的分子生物学机制至今尚未完全阐明.近年研究表明,高迁移率蛋白-1(high mobility group box 1,HMGB1)是一种新的“晚期”致炎细胞因子参与冠心病的致病过程,在心血管病中的作用越来越受到人们的重视[2-3].本研究观察HMGB1在不同类型冠心病患者的表达及意义,探讨对冠心病预后的预测作用.

MicroRNAs are widely involved in the pathogenesis of cardiovascular diseases through regulating gene expression via translational inhibition or degradation of their target mRNAs. Recent studies have indicated a critical role of microRNA-206 in myocardial ischaemia-reperfusion (I/R) injury. However, the function of miR-206 in myocardial I/R injury is currently unclear. The present study was aimed to identify the specific role of miR-206 in myocardial I/R injury and explore the underlying molecular mechanism. Our results revealed that the expression level of miR-206 was significantly decreased both in rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation (H/R) compared with the corresponding control. Overexpression of miR-206 observably decreased infarct size and inhibited the cardiomyocyte apoptosis induced by I/R injury. Furthermore, bioinformatics analysis, luciferase activity and western blot assay proved that Gadd45β (growth arrest DNA damage-inducible gene 45β) was a direct target gene of miR-206. In addition, the expression of pro-apoptotic-related genes, such as p53, Bax and cleaved caspase3, was decreased in association with the down-regulation of Gadd45β. In summary, this study demonstrates that miR-206 could protect against myocardial I/R injury by targeting Gadd45β.