m6A甲基化在心肌缺血再灌注与心肌再生中的研究进展

N6-甲基腺嘌呤(N6-methyladenosine, m⁶A)RNA甲基化是最常见的、动态的、可逆的表观遗传RNA修饰，参与了包括心血管疾病在内的多种人类疾病的发病机制。最近的研究表明，m⁶A RNA甲基化在心肌缺血再灌注及心脏再生中发挥重要调控作用。重要的是，这些新发现表明，通过改变m⁶A的调节因子来控制m⁶A的水平，可能是防止心脏功能恶化促进心脏修复的一种新颖而有力的策略。     

N6-甲基腺苷修饰与心血管疾病关系研究

N⁶-甲基腺苷(m⁶A)修饰是一种原核生物和真核生物中广泛存在的转录后RNA修饰,涉及多种类型的RNA。在信使RNA中,m⁶A修饰可以影响包括二级结构、亚细胞定位、核转运、翻译和降解等信使RNA的加工和代谢。m⁶A修饰在疾病诊断、疗效评估和预后判断等方面具有突出优势。现总结当前文献对于m⁶A修饰的认识,简述其在心血管疾病中的最新研究进展。     

RNA甲基化修饰在肺动脉高压中作用机制研究进展

肺动脉高压(PAH)是一类多病因引起的以肺血管重构为主要特征，并最终引起右心衰竭和过早死亡的临床综合征。尽管PAH临床诊治取得明显进展，但疗效仍不能令人满意，患者5年生存率较低，且其发病机制复杂，目前仍未完全阐明。RNA甲基化修饰作为表观遗传学修饰中的第三大研究领域，其主要通过甲基转移酶(Writers)、去甲基化酶(Erasers)和甲基识别蛋白(Readers)三类蛋白可逆地写入、移除和读取甲基，在不改变基因序列的情况下对细胞增殖、凋亡、代谢等细胞生物学行为发挥重要作用。RNA甲基化修饰在肿瘤、心血管疾病、免疫与代谢性疾病等的发生发展中起着关键的调节作用，此外，其也参与了PAH的发生发展，并给PAH的治疗带来了新的希望。本研究综述了RNA甲基化修饰的种类及作用，N⁶-甲基腺嘌呤(m⁶A)、5-甲基胞嘧啶(m⁵C)和7-甲基鸟苷(m⁷G)修饰在PAH中的作用机制，以期为研究者提供新思路。     

经典组蛋白去乙酰化酶在中枢神经系统中作用

<正>表观遗传学是指不改变脱氧核糖核酸(DNA)序列而产生的可遗传变化,其在调节基因组功能中发挥关键作用,影响基因表达和(或)转录,从而调控机体的生长、发育及病理过程^[1]。表观遗传学修饰主要包括DNA甲基化、组蛋白修饰和非编码核糖核酸(RNA)等。组蛋白乙酰化核酸修饰是调节DNA功能的重要方式,近年来,研究表明组蛋白乙酰化在神经系统疾病发生发展中起重要作用^[2]。     

动脉粥样硬化的表观遗传调控

表观遗传调控指的是在DNA序列不变的情况下基因表达发生的可遗传性改变。目前,已知的表观遗传调控的主要机制包括DNA甲基化、组蛋白修饰和非编码RNA。大量研究证实,在心血管疾病、肿瘤和自身免疫性疾病等方面表观遗传调控发挥着重要作用。近年来,越来越多的研究表明,表观遗传调控在动脉粥样硬化的疾病病程中发挥着重要作用。本文将围绕DNA甲基化、组蛋白修饰和非编码RNA这三种主要的表观遗传调控对血管平滑肌细胞的调节来探讨表观遗传调控在动脉粥样硬化进程中的重要作用。     

m6A甲基化修饰在消化系统恶性肿瘤免疫治疗中的研究进展

N⁶-甲基腺苷(m⁶A)作为转录表达的关键调节剂,是真核细胞中最为常见的表观转录组学修饰。通过三大调节因子甲基转移酶、去甲基化酶和结合蛋白的共同调节,m⁶A在肿瘤的发生、发展中起有重要作用。免疫治疗作为多种晚期恶性肿瘤的一线治疗方案,在许多消化系统恶性肿瘤患者中表现出明显的耐药性。最近的研究证实,m⁶A甲基化修饰对肿瘤免疫起有重要的调节作用,从而影响肿瘤患者免疫治疗的疗效。本文就m⁶A甲基化修饰在消化系统恶性肿瘤免疫治疗中的研究进展作一综述。     

METTL3在心血管疾病中的作用机制研究进展

近年来,由于RNA的甲基化修饰在基因转录后调控中发挥重要作用而引起人们高度关注。其中,RNA的N6甲基腺苷(m6A)修饰是mRNA中除5′帽子结构外含量最高的甲基化修饰。调控m6A修饰的酶分为三大类：RNA甲基转移酶、RNA去甲基化酶和RNA甲基化识别酶,它们分别对RNA的N6-腺苷酸起着催化甲基化修饰、去除甲基化修饰及识别甲基化位点的作用,进而参与下游翻译、RNA降解、控制RNA出核速度等过程。在这些酶中,METTL3作为RNA的甲基转移酶核心成分,具有调控细胞RNA整体m6A修饰的作用。心血管疾病是一类受后天环境因素影响较大的疾病,而后天环境因素通常可以通过表观遗传学的相关机制影响疾病的发生发展,故以转录后调控为核心的表观遗传学在心血管疾病研究中成为热门话题。本综述旨在对近几年与METTL3在心血管疾病中的相关研究进行简单整理总结,有望帮助后续的基础科研和临床工作者了解RNA的m6A修饰在心血管疾病发生发展机制中的研究进展。     

DNA甲基化与心血管疾病研究进展

心血管疾病严重威胁人类健康,其发生发展是遗传因素和环境因素相互作用的复杂过程。表观遗传修饰是连接环境与遗传因素的桥梁。表观遗传包括DNA甲基化、基因组印记、染色质组蛋自修饰、RNA编辑等各种基因调控方式。近些年研究发现表观遗传在心血管疾病的发生发展中起着重要的作用。初步的研究发现动脉粥样硬化、高血压病、肥厚性心肌病和心律失常等相关候选基因表达和DNA甲基化修饰之间有一定的关联性,如雌激素受体(ER)基因甲基化异常可能参与动脉粥样硬化的发生,血管紧张素I b型受体(AT1b)编码的基因低甲基化与高血压发病可能相关,血浆血栓调节蛋白(TM)启动子区高甲基化状态可能介导冠心病的发病等。本文就近年来心血管疾病中DNA甲基化的作用的研究进展进行综述。     

m6A甲基化修饰在动脉粥样硬化中的作用

N6-甲基嘌呤(m⁶A)是真核生物中最常见的转录后RNA修饰类型,涉及多种类型RNA。m⁶A甲基化修饰是动态可逆的,主要由多种酶和蛋白进行调控,包括甲基转移酶、去甲基化酶和m⁶A相关结合蛋白。动脉粥样硬化是心脑血管疾病的主要原因。近期研究发现m⁶A甲基化修饰与动脉粥样硬化密切相关。该文总结了目前对m⁶A甲基化修饰机制的认识,并阐述了与动脉粥样硬化相关细胞中m⁶A甲基化修饰的机制及最新进展,为动脉粥样硬化的诊断和防治提供新靶点。     

表观遗传学和肾脏疾病

表观遗传学是研究基因的核苷酸序列不发生改变的情况下发生可遗传修饰的一门学科。表观遗传机制包括DNA甲基化、组蛋白修饰、基因组印记、母体效应、基因沉默和非编码RNA的调控作用等。目前,对于表观遗传学的研究主要集中在DNA甲基化、组蛋白修饰和非编码RNA的调控上,其机制在肾脏疾病的发生和发展中亦起重要作用。     

非酒精性脂肪性肝炎患者外周血跨膜蛋白6超家族成员2基因表达与心血管疾病的关系

目的 探究非酒精性脂肪性肝炎(NASH)患者跨膜蛋白6超家族成员2(TM6SF2)基因表达与心血管疾病(CVD)的关系.方法 2018年9月～2020年9月我院收治的93例NASH患者,根据其是否合并CVD分为NASH组及CVD组,应用TaqMan探针法检测两组患者的TM6SF2基因rs58542936位点多态性,采用...     

N6-甲基腺苷甲基化在射血分数保留性心力衰竭中的作用的研究进展

表观遗传学参与心血管疾病进展的过程。近年研究表明,射血分数保留性心力衰竭(HFpEF)患者的多个基因转录本存在N⁶-甲基腺苷(m⁶A)水平的改变。现介绍m⁶A及其调节因子(甲基化酶、去甲基化酶和甲基化阅读蛋白)与HFpEF的关系,说明m⁶A可能通过影响心肌肥厚与纤维化、细胞自噬、炎症与氧化应激、糖脂代谢参与HFpEF的发生和发展,以期为HFpEF的治疗靶点提供新的研究方向。     

Cardiometabolic disease in South Asians: A global health concern in an expanding population

Cardiovascular disease (CVD) is one of the main causes of mortality and morbidity worldwide. As an emerging population, South Asians (SAs) bear a disproportionately high burden of CVD relative to underlying classical risk factors, partly attributable to a greater prevalence of insulin resistance and diabetes and distinct genetic and epigenetic influences. While the phenotypic distinctions between SAs and other ethnicities in CVD risk are becoming increasingly clear, the biology of these conditions remains an area of active investigation, with emerging studies involving metabolism, genetic variation and epigenetic modifiers (e.g., extracellular RNA). In this review, we describe the current literature on prevalence, prognosis and CVD risk in SAs, and provide a landscape of translational research in this field toward ameliorating CVD risk in SAs.     

Antiremodeling effects on the left ventricle during beta-blockade with metoprolol in the treatment of chronic heart failure

OBJECTIVES

The purpose of the study was to investigate the effects of beta₁-blockade on left ventricular (LV) size and function for patients with chronic heart failure.

BACKGROUND

Large-scale trials have shown that a marked decrease in mortality can be obtained by treatment of chronic heart failure with beta-adrenergic blocking agents. Possible mechanisms behind this effect remain yet to be fully elucidated, and previous studies have presented insignificant results regarding suspected LV antiremodeling effects.

METHODS

In this randomized, placebo-controlled and double-blind substudy to the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF), 41 patients were examined with magnetic resonance imaging three times in a six-month period, assessing LV dimensions and function.

RESULTS

Decreases in both LV end-diastolic volume index (150 ml/m² at baseline to 126 ml/m² after six months, P = 0.007) and LV end-systolic volume index (107 ml/m² to 81 ml/m², P = 0.001) were found, whereas LV ejection fraction increased in the metoprolol CR/XL group (29% to 37%, P = 0.005). No significant changes were seen in the placebo group regarding these variables. Left ventricular stroke volume index remained unchanged, whereas LV mass index decreased in both groups (175 g/m² to 160 g/m² in the placebo group [p = 0.005] and 179 g/m² to 164 g/m² in the metoprolol CR/XL group [p = 0.01]).

CONCLUSIONS

This study is the first randomized study to demonstrate that the beta₁-blocker metoprolol CR/XL has antiremodeling effects on the LV in patients with chronic heart failure and consequently provides an explanation for the highly significant decrease in mortality from worsening heart failure found in the MERIT-HF trial.     

慢加急性肝衰竭患者第三腰椎骨骼肌指数与临床指标的关系*

目的 观察慢加急性肝衰竭(ACLF)患者第三腰椎骨骼肌指数(L3-SMI)及其与临床指标的关系。方法 2015年1月～2019年6月我院收治的126例住院期间完善了腹部CT或MRI检查的ACLF患者,计算L3-SMI,比较不同L3-SMI水平患者的临床特点。结果 入组患者男性113例,女性13例;男性患者L3-SMI为(40.3±7.4)cm²/m²,显著大于女性患者[(33.9±4.5)cm²/m²,P＜0.05];在男性患者中,有肝硬化基础者L3-SMI为(38.1±5.9)cm²/m²,显著低于无肝硬化基础者[(42.0±7.9)cm²/m², P＜0.05];酒精性肝病患者L3-SMI为(34.8±6.8)cm²/m²,显著低于非酒精性肝病患者[(41.5±7.0)cm²/m², P＜0.05];90 d生存组患者L3-SMI为(40.7±7.7)cm²/m²,与90 d死亡患者[(38.8±6.3)cm²/m², P＞0.05]比,差异无统计学意义;将男性患者分为低L3-SMI组(≤40 cm²/m²)61例和高L3-SMI组(＞40 cm²/m²)52例,结果低L3-SMI组和高L3-SMI组患者肝性脑病发生率分别为19.7%和13.5% (P＞0.05),低L3-SMI组90 d生存率为68.9%,与高L3-SMI组的76.9%(P＞0.05)比,差异无统计学意义;高L3-SMI组患者体质指数为(24.5±3.9)kg/m²,显著高于低L3-SMI组[(20.5±2.9)cm²/m², P＜0.05];高L3-SMI组患者血红蛋白为(126.4±23.2)g/L,显著高于低L3-SMI组[(114.7±21.3)g/L, P＜0.05];高L3-SMI组患者血钠为(136.6±4.1)g/L,显著高于低L3-SMI组[(133.5±4.5)g/L, P＜0.05];低L3-SMI组和高L3-SMI组患者血清总胆红素分别为[(437.1±198.3)μmol/L和(317.4±173.0)μmol/L,P＜0.05],差异显著。结论 女性患者、低体质量患者、肝硬化患者、酒精性肝病患者L3-SMI水平更低,ACLF患者L3-SMI水平与病情严重程度呈负相关,与疾病转归存在一定的相关性,但需进一步扩大样本进行验证。     

Effects of intravenously administered digoxin on mild left ventricular failure in acute myocardial infarction in man

Studies were made in 10 patients with early mild left ventricular failure in acute myocardial infarction to determine the hemodynamic correlates of the condition and evaluate the effects of intravenously administered digoxin. Studies were performed within 72 hours of infarction. Patients with basilar rales, tachycardia and ventricular (S₃) gallop sound were selected for study. Findings during the control period were consistent with mild left ventricular failure. Stroke index was below normal (28 ± 7.1 ml/m²), but cardiac index was within normal limits (3.22 ± 0.60 liters/min per m²) because of tachycardia. Stroke work index was low (39 +- 13.7 g-m/m²), and pulmonary arterial end-diastolic pressure was minimally increased (15.2 ± 3.5 mm Hg).

After intravenous administration of digoxin (0.75 mg in 7 patients, 1.0 mg in 3 patients), there were no statistically significant changes in any of the measured variables when the whole group was considered. Relating stroke work index to pulmonary arterial diastolic pressure, 2 types of responses were found. Four patients had a distinct inotropic response; the other 6 patients had no significant change, or a worsening of function. The reasons for a variable response in the early phase of infarction may be related to the regional nature of infarction or possibly to humoral factors influencing myocardial performance. Data suggest that digitalis is of limited value during this stage of infarction. Further studies and more precise characterization of patients may provide insight into the role of digitalis in the early phases of acute infarction.     

Role of mi RNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer

Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic mi RNAs and downregulated tumour-suppressor mi RNAs in this type of cancer. In this review, we provide an overview of the role of mi RNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on mi RNA activity.     

Hormone replacement therapy and cardiovascular risk in menopausal women

The incidence of cardiovascular disease (CVD) differs markedly with regard to gender and age. Women have CVD 10 years later than men. Estrogen seems to play a key role in mediating the risk of CVD in women. The relative risk of CVD is lower in women before menopause and equals that of men between the 6th and 7th decade. However the effects of hormone replacement therapy (HRT) on cardiovascular morbidity and/or mortality in postmenopausal women remain controversial. The results of observational studies and randomized trials in post menopausal women are reviewed in this article. They point out the absolute need of large scale prospective randomized clinical studies to quantify the effects of HRT for primary and secondary prevention of cardiovascular disease in particular in non American countries.     

The role of electronegative low-density lipoprotein in cardiovascular diseases and its therapeutic implications

Cardiovascular disease (CVD) is a health problem of great concern to both the public and medical authorities. Low-density lipoprotein (LDL) has been reported to play an important role in both the development and progression of CVD, but studies are underway to determine how LDL exerts its effects. In recent years, it has been found that LDL has several subfractions, each of which affects endothelial function differently; L5, the most electronegative fraction, has been shown to be unique in that it induces an atherogenic response. This review examines the current knowledge concerning the relationships between L5 and CVD and highlights the role of L5 in the pathophysiology of CVD, especially with regards to atherosclerosis.