血管紧张素Ⅱ对单核/巨噬细胞的致炎作用及其药物干预

动脉粥样硬化斑块形成和破裂的重要原因是病变部位炎症反应的加剧,而巨噬细胞作为粥样斑块内主要的炎症细胞,在炎症反应中起主导作用.血管紧张素Ⅱ作为一种重要促炎因子,促进单核/巨噬细胞浸润于动脉粥样硬化斑块,激活斑块内的巨噬细胞,上调各种炎症因子,从而参与动脉粥样硬化的发生发展过程.血管紧张素转化酶抑制剂、AngⅡ受体阻断剂、调血脂药、干扰素-β、雌激素等药物可减轻血管紧张素Ⅱ诱导的血管壁炎症反应,发挥抗动脉粥样硬化作用.     

胆固醇结晶激活动脉粥样硬化斑块巨噬细胞NLRP3炎症体的途径

动脉粥样硬化既是胆固醇在血管壁聚集的疾病,也是发生在动脉壁的一种低强度慢性炎症形式。近年来有研究证实胆固醇结晶在动脉粥样硬化发生发展中具有重要作用。新的显微技术证实,胆固醇结晶在动脉粥样硬化斑块形成的早期即已出现,并与早期炎症有关。胆固醇结晶通过诱发局部炎症,促进大的脂质核心形成;刺破纤维帽,导致斑块破裂进而促进动脉粥样硬化斑块的进展。在影响斑块进程中,NLRP3炎症体的激活对此发挥了重要的作用。NLRP3炎症体是研究最多最明确的炎症体,其与非炎症性疾病的发生发展密切相关。以胆固醇结晶激活NLRP3炎症体的途径作为研究靶点,为动脉粥样硬化的诊断和治疗提供了新的思路和方法。该文就胆固醇结晶在动脉粥样硬化斑块中激活巨噬细胞NLRP3炎症体的两种途径做一综述。     

单核细胞及其来源细胞在动脉粥样硬化炎症发病机制中的作用

心血管疾病尤其是冠状动脉粥样硬化心脏病,已经成为威胁人类健康的主要杀手。但是由于动脉粥样斑块形成的复杂性,动脉粥样硬化发生机制并不明确,该疾病发生的炎症学说成为研究热点。本文将对单核细胞及其来源的巨噬细胞和树突状细胞在动脉粥样硬化炎症发病机制中的作用做一综述,为寻找该疾病新的药物靶点提供思路。     

脂蛋白与冠心病

冠心病绝大多数由动脉粥样硬化引起,而动脉粥样硬化的形成与消退均与血浆脂蛋白有密切关系。近年上述两者的关系已不断得到阐明,不仅血浆低密度脂蛋白浓度的增高可引起动脉粥样斑块的形成,且高密度脂蛋白浓度的降低亦与动脉粥样斑块的产生有关。此外,低密度脂蛋白(LDL)受体缺陷已被认为是家族性高胆固醇血症的原因。本文以脂蛋白为中心就血脂与脂蛋白的关系、高脂蛋白血症,动脉粥样硬化病变的预防,动脉粥样斑块的消退等四个方面探讨了动脉粥样硬化的发病原理与冠心病的防治问题。     

巨噬细胞移动抑制因子及其在动脉粥样硬化中的作用

巨噬细胞移动抑制因子（macrophage migration inhibitory factor,MIF）,其主要作用为抑制巨噬细胞的游走移动、促进巨噬细胞在炎症局部浸润、聚集、激活及分泌一些细胞因子,如IL-1、TNF—α、NO等,从而间接增强巨噬细胞的功能。巨噬细胞不仅是产生MIF的主要细胞,也是MIF作用的靶细胞,因此MIF在巨噬细胞参与调节的各种疾病尤其是动脉粥样硬化中发挥着重要作用。研究表明,血管发生动脉粥样硬化部位的MIF表达水平明显上调,且随着斑块的发展逐渐上升;相反,阻断MIF的表达则可以显著廷缓动脉粥样硬化的发撮并稳定斑块。因此,MIF在单核巨噬细胞的血管粘附、跨膜移动、内皮下聚集、泡沫细胞的形成及斑块稳定中的作用可能与动脉粥样硬化的发生和发展有密切关系。本文将主要就MIF的生理及病理生理学功能特别是其在动脉粥样硬化发病及治疗中的作用作一综述。     

脂联素抗冠状动脉粥样硬化机制的研究进展

脂联素是近年来发现的具有抗冠状动脉粥样硬化作用的脂肪因子,它是脂肪细胞分泌的一种蛋白质,分别在粥样斑块形成早期、粥样斑块形成过程中和粥样斑块的稳定性等多个方面发挥抗粥样硬化的作用.脂联素的抗粥样硬化机制是一个复杂的病理生理机制,包括维护动脉内皮细胞的正常功能、抑制巨噬细胞和平滑肌细胞的迁移和增生、稳定粥样斑块等.脂联素的抗动脉粥样硬化作用显示了巨大的临床应用潜力.     

巨噬细胞胆固醇转运相关蛋白研究进展

动脉粥样斑块中泡沫细胞的形成与巨噬细胞胆固醇的转运密切相关,巨噬细胞胆固醇转运是胆固醇逆转运中的一个重要过程,它可清除外周组织过多的胆固醇,对维持细胞内胆固醇稳定、延缓动脉粥样硬化的发生发展有着重要意义.这个过程涉及到许多转运相关蛋白的作用,如三磷酸腺苷结合盒转运体A1/G1、载脂蛋白A-Ⅰ、胆固醇脂转运蛋白、卵磷脂胆固醇酰基转移酶等.本文就巨噬细胞胆固醇转运过程中相关蛋白的作用做一综述,以期为动脉粥样硬化相关疾病的防治研究提供新的思路.     

慢性炎症、自身免疫和动脉粥样硬化

动脉粥样硬化是一种炎症性疾病。在粥样斑块中存在许多免疫细胞,而且在不稳定斑块中尤为丰富。近年来对动脉粥样硬化中免疫细胞的聚集,分化和激活有了更深入的了解。流行病研究发现了多种与其相关的病毒和细菌感染。通过研究初步研究了几个自身性抗原,并提出了自身免疫假说。根据这些新的认识,提出了免疫调节和预防接种等心血管疾病的预防和治疗策略。这必将极大地提高对动脉粥样硬化的研究和防治水平。     

亚毒性剂量毒死蜱降低新西兰兔ABCA1表达加重高脂诱导的动脉粥样硬化

为了探讨亚毒性剂量有机磷酸酯杀虫剂毒死蜱对高脂饮食诱导的动脉粥样硬化的影响及其机制,32只健康雄性新西兰兔随机分为对照组、毒死蜱组、高脂组、高脂+毒死蜱组.每天以20 mg/kg亚毒性剂量的毒死蜱灌胃处理6个月.动物处死后检测血脂水平和血清胆碱酯酶活性.收集腹腔巨噬细胞,测定其胆固醇流出率.苏丹Ⅳ染色观察胸主动脉粥样硬化斑块,定量分析动脉粥样硬化斑块占血管内表面积的百分比.颈总动脉石蜡切片,观察动脉粥样硬化斑块.采用实时定量PCR和蛋白质印迹检测,分别检测肝脏、血管和腹腔巨噬细胞中三磷酸腺苷结合盒转运体A1(ATP-binding cassette transporter A1,ABCA1)mRNA和蛋白质的表达.结果显示:与对照组相比,高脂饮食升高了血清总胆固醇和脂蛋白水平,主动脉和颈总动脉出现明显的动脉粥样硬化斑块,其肝脏、主动脉和腹腔巨噬细胞ABCA1的表达升高,腹腔巨噬细胞中胆固醇流出增加;与对照组相比,毒死蜱组血清胆碱酯酶活性降低,但没有出现明显的中毒症状和肝肾功能损伤,血清中高密度脂蛋白(HDL)水平降低,ABCA1的表达降低,腹腔巨噬细胞中胆固醇流出减少;高脂+毒死蜱组与高脂组相比,血清胆碱酯酶活性降低,也没有出现明显的中毒症状和肝肾功能损伤,ABCA1的表达降低,腹腔巨噬细胞中胆固醇流出减少,主动脉和颈总动脉粥样硬化斑块更加明显.结果提示长期暴露于亚毒性剂量的毒死蜱可加速高脂饮食的致动脉粥样硬化作用,其机制可能与毒死蜱降低体内ABCA1的表达和胆固醇流出有关.     

热休克蛋白在动脉粥样硬化发生发展中作用的研究进展

近年来研究表明热休克蛋白与动脉粥样硬化有密切联系,以HSP60为代表的热休克蛋白通过诱导自身免疫,增强炎症反应,促进血管平滑肌细胞增殖、迁移,促进动脉粥样硬化的发生发展;以HSP27为代表的热休克蛋白可以抑制氧化应激,降低炎症免疫反应,抑制血管平滑肌的增殖、迁移、凋亡,增加动脉粥样斑块的稳定性,抑制动脉粥样硬化的进展。这些热休克蛋白作用的新认识对动脉粥样硬化诊断和治疗提供了有益的线索。     

中性粒细胞与淋巴细胞比值和冠心病的关系

炎性作用在心血管疾病中的作用越来越重要,尤其是炎性标记物与冠心病之间的相互作用及关系,近年来被广泛研究,大多研究结果呈现一致性。中性粒细胞与淋巴细胞比值是近些年新兴的炎症标记物,其简易、普及、易获取的特点受到了广泛学者的肯定。NLR与动脉粥样硬化相关,相关研究显示动脉僵硬度、钙化积分与NLR密切相关,另外,高NLR者更易发现易损斑块。NLR可预测急性冠脉综合征的短期及长期心血管事件发生率及死亡率,以及预测稳定性心绞痛预后情况及侧支循环是否丰富。在冠脉造影的应用中,发现NLR不仅与冠脉病变严重程度密切相关,能预测完全闭塞病变的发生,及预测无复流的发生。在已有心血管危险因素的基础上,NLR可作为新成员,为冠心病的发现及其预后的风险评价提供依据。     

冠状动脉磁共振血管成像和CT对可疑冠心病患者心脏事件的预测价值的比较研究

摘要 目的：探讨与比较冠状动脉核磁共振(MR)血管成像和CT对可疑冠心病患者心脏事件的预测价值。方法：2018年4月到2020年10月选择在本院诊治的103例可疑冠心病患者作为研究对象,所有患者都给予冠状动脉MRI血管成像与64层螺旋CT冠状动脉成像检查,记录影像学特征。随访患者的预后并进行预测价值分析。结果：103例可疑冠心病患者随访到2021年4月1日,发生心血管不良终点事件23例(不良事件组),发生率为22.3%。不良事件组的MRI血管成像显示右冠状动脉血管长度与内径都低于非不良事件组(P<0.05)。不良事件组的CT显示斑块率、斑块性质等与非不良事件组对比差异有统计学意义(P<0.05),两组斑块位置对比差异无统计学意义(P>0.05)。多因素Cox回归分析显示斑块性质、斑块率、右冠状动脉血管长度与内径都为导致心血管不良终点事件的重要因素(P<0.05)。结论：冠状动脉MRI血管成像和CT都可有效预测可疑冠心病患者心脏事件发生情况,能满足临床诊断可疑冠心病与预测预后的要求。     

肥大细胞在动脉粥样硬化形成中的作用

动脉粥样硬化,是冠心病的病理基础,被认为是一种慢性炎症性疾病,涉及如巨噬细胞和T淋巴细胞等许多炎性细胞。肥大细胞是一种重要的免疫细胞,其功能主要是在超敏反应方面的作用。有病理学研究表明：肥大细胞在动脉粥样硬化斑块周围表达增加,这表明肥大细胞可能与疾病的进展有关。最近的研究表明,肥大细胞在动脉粥样硬化中确实起着重要的作用。本文通过总结肥大细胞在动脉粥样硬化形成中的作用,为在疾病进程中,通过调节肥大细胞功能来改善动脉粥样硬化的这种治疗方式的可能性提供依据。     

Macrophages heterogeneity in atherosclerosis – implications for therapy

Atherosclerosis is a chronic inflammatory disease occurring within the artery wall and is an underlying cause of cardiovascular complications, including myocardial infarction, stroke and peripheral vascular disease. Its pathogenesis involves many immune cell types with a well accepted role for monocyte/macrophages. Cholesterol-loaded macrophages are a characteristic feature of plaques and are major players in all stages of plaque development. As well as modulating lipid metabolism, macrophages secrete inflammatory cytokines, chemokines and reactive oxygen and nitrogen species that drive pathogenesis. They also produce proteases and tissue factor that contribute to plaque rupture and thrombosis. Macrophages are however heterogeneous cells and when appropriately activated, they phagocytose cytotoxic lipoproteins, clear apoptotic bodies, secrete anti-inflammatory cytokines and synthesize matrix repair proteins that stabilize vulnerable plaques. Pharmacological modulation of macrophage activity therefore represents a potential therapeutic strategy for atherosclerosis. The aim of this review is to provide an overview of the current understanding of the different macrophage subsets and their monocyte precursors, and, the implications of these subsets for atherosclerosis. This will present a foundation for highlighting novel opportunities to exploit the heterogeneity of macrophages as important diagnostic and therapeutic targets for atherosclerosis and its associated diseases.     

LOX-1, a new marker of risk and prognosis in coronary artery disease?

The development of atherosclerosis is caused by the accumulation of lipid, inflammatory cytokine production, and the large amount of inflammatory cells in the arterial wall. It is now established that the presence of oxidized low-density lipoproteins (ox-LDL) has an important role in the pathogenesis of the disease. There are many scavenger receptors for ox-LDL, among which LOX-1 seems to be important for the induction of endothelial dysfunction and the other subsequent events that lead to the formation of atheromatous plaque. Our findings indicate the presence of a regulatory role induced by the presence of ox-LDL on LOX-1 through the amplification of IL-6 synthesis. This mechanism contributes to the upregulation of the ORL-1 gene expression in presence of risk factors. Many authors have shown the possibility to use LOX-1 as a good marker for the diagnosis and prognosis of coronary artery disease because it is easy to measure and more sensitive than other markers commonly used in the routine of laboratory medicine.     

宝石能谱CT 冠脉成像在隐匿型冠心病冠状动脉粥样斑块性质判断中的价值

目的:探讨宝石能谱CT冠脉成像在隐匿型冠心病冠状动脉粥样斑块性质判断中的价值,为临床隐匿型冠心病的诊断和治疗提供影像学参考依据。方法:选择2014年6月~2015年6月在我院诊断为心肌缺血且无临床症状的隐匿型冠心病患者共360例,所有入选患者均行宝石能谱CT冠脉成像检查,其中155例有冠状动脉狭窄,且伴有不同性质的粥样斑块。分析冠状动脉不同血管狭窄情况、斑块分型和斑块数目。结果:所有冠脉动脉狭窄均为轻度狭窄和中度狭窄,主要集中在左主干和左前降支,分别占35.48%和37.42%。硬斑块数目最多,占75.43%,其次为混合斑块和软斑块,分别占16.19%和8.38%。冠状动脉4支血管粥样斑块均为硬斑块者最多(29.03%)、硬斑块与软斑块同时存在者占29.03%、硬斑块与软斑块、混合斑块同时存在者占14.84%,未见单纯混合斑块或软斑块的患者。结论:隐匿型冠心病患者冠状动脉狭窄主要为轻、中度狭窄,冠状动脉斑块以硬斑块为主。宝石能谱CT冠脉成像能准确的判断隐匿型冠心病冠状动脉粥样斑块性质,值得临床推广借鉴。     

Inflammatory markers: linking unstable plaques to coronary event, an interventional perspective

Abundant data links inflammatory mechanisms to atheromatous plaque destabilization leading to plaque rupture and coronary events. The discovery of inflammatory cells and inflammatory mediators within atherosclerotic plaques prone to rupture led to a series of studies demonstrating an association between various markers of inflammation and future coronary events. Inflammatory markers have also been used in patients undergoing coronary angioplasty in an attempt to predict restenosis and risk for post-procedural coronary events. This review article provides an overview on the potential use of inflammatory markers in the context of coronary interventions.     

Vascular damage as an underlying mechanism of cardiac and cerebral toxicity in irradiated cancer patients

Radiation is an independent risk factor for cardiovascular and cerebrovascular disease in cancer patients. Modern radiotherapy techniques reduce the volume of the heart and major coronary vessels exposed to high doses, but some exposure is often unavoidable. Radiation damage to the myocardium is caused primarily by inflammatory changes in the microvasculature, leading to microthrombi and occlusion of vessels, reduced vascular density, perfusion defects and focal ischemia. This is followed by progressive myocardial cell death and fibrosis. Clinical studies also demonstrate regional perfusion defects in non-symptomatic breast cancer patients after radiotherapy. The incidence and extent of perfusion defects are related to the volume of left ventricle included in the radiation field. Irradiation of endothelial cells lining large vessels also increases expression of inflammatory molecules, leading to adhesion and transmigration of circulating monocytes. In the presence of elevated cholesterol, invading monocytes transform into activated macrophages and form fatty streaks in the intima, thereby initiating the process of atherosclerosis. Experimental studies have shown that radiation predisposes to the formation of inflammatory plaque, which is more likely to rupture and cause a fatal heart attack or stroke. This paper presents a brief overview of the current knowledge on mechanisms for development of radiation-induced cardiovascular and cerebrovascular damage. It does not represent a comprehensive review of the literature, but reference is made to several excellent recent reviews on the topic.     

The molecular role of mast cells in atherosclerotic cardiovascular disease

Human atherosclerosis has many characteristics of an inflammatory disorder. Recent data suggest that mast cells might be important in the pathogenesis of atherosclerotic disease. By secretion of pro-inflammatory cytokines, mast cells can assist in the recruitment of monocytes and lymphocytes into vascular tissue, thereby propagating the inflammatory response. Mast cell enzymes might activate pro-metalloproteinases, thereby destabilizing atheromatous plaques. Mast cells can facilitate foam cell formation by promoting cholesterol accumulation. However, mast cell tryptase could slow thrombus formation at sites of plaque rupture by interfering with coagulation. Therefore, mast cells can modulate coronary artery disease by both facilitatory and inhibitory pathways.     

Recent insights into atherosclerotic plaque cell autophagy

Cardiovascular and cerebrovascular diseases, such as coronary heart disease and stroke, caused by atherosclerosis have become the “number one killer”, seriously endangering human health in developing and developed countries. Atherosclerosis mainly occurs in large and medium-sized arteries and involves intimal thickening, accumulation of foam cells, and formation of atheromatous plaques. Autophagy is a cellular catabolic process that has evolved to defend cells from the turnover of intracellular molecules. Autophagy is thought to play an important role in the development of plaques. This review focuses on studies on autophagy in cells involved in the formation of atherosclerotic plaques, such as monocytes, macrophages, endothelial cells, dendritic cells, and vascular smooth muscle cells, indicating that autophagy plays an important role in plaque development. We mainly discuss the roles of autophagy in these cells in maintaining the stability of atherosclerotic plaques, providing a reference for the next steps to unravel the mechanisms of atherogenesis.