炎性体在动脉粥样硬化等心血管疾病中的作用及机制

炎性体是一个识别多种固有免疫系统激活物的多蛋白复合体,它可以促进白细胞介素1β（IL-1β）和白细胞介素18（IL-18）等炎症因子的生成,参与多种心血管疾病（CVD）的炎症反应,如动脉粥样硬化、缺血性心脏病、缺血再灌注损伤、高血压和心肌病变等。炎性体激活及其下游产物生成的调控机制已成为CVD研究领域新的热点。此外,炎性体作为固有免疫系统的一部分,为CVD治疗提供了新的药物靶点。     

单核巨噬细胞系统在心肌损伤和修复中的作用研究进展

心力衰竭（简称心衰）是各种心血管疾病发展的最后阶段,已成为世界范围内的主要公共卫生问题。慢性心衰的基本病因是各种原因所致的心肌损伤,如心肌梗死、心肌肥厚、心肌炎等,造成心肌结构及功能改变,最终发展为心衰。这些心肌损伤可分为缺血性心肌损伤和非缺血性心肌损伤。越来越多的证据表明,免疫炎症细胞,尤其是单核巨噬细胞,在心肌损伤修复中发挥着重要的作用。本文就单核巨噬细胞在心肌损伤和修复中的作用及其研究进展进行综述。     

急性缺血性卒中与氧化应激、炎症反应标志物

已有研究表明氧化应激和炎症反应在动脉粥样硬化形成、急性脑卒中临床事件发生以及缺血损伤后侧枝循环建立等代偿机制中发挥重要作用,因此抗氧化应激及抑制炎症反应成为防治动脉粥样硬化以及急性缺血性卒中的重要措施之一.目前已有多种血液标志物被用于研究其变化情况,但还没有明确何种标志物具有更高的敏感性和特异性,本文选取几个研究较充分的血液标志物,就其作用机制及与预后关系的研究做一综述.     

免疫/炎症反应在狼疮患者冠心病中的作用

冠心病是造成系统性红斑狼疮患者死亡的主要原因,系统性红斑狼疮失调的免疫/炎症反应会增加动脉粥样硬化疾病和血管损伤的风险。免疫/炎症反应介导的血管内皮损伤和动脉粥样硬化保护机制受损是动脉粥样硬化性心脏病形成的中心环节。现概述流行病学并讨论系统性红斑狼疮患者的免疫/炎症反应在冠心病发病机制中的作用。     

miR-155与缺血性脑卒中关系的研究进展

缺血性脑卒中发病率较高,其高致残率影响病人的生存质量,动脉粥样硬化是缺血性脑卒中的主要病因。microRNA作为一类内源性小分子RNA在脑血管疾病中参与调控炎症反应、细胞损伤等病理过程,其中miR-155认为在脑血管疾病的发生中发挥了重要的调控作用。基于miR-155在动脉粥样硬化及缺血性脑卒中病人与动物实验模型中的表达情况,综述miR-155与动脉粥样硬化及缺血性脑卒中的关系,为缺血性脑卒中的预防、治疗及预后的评估提供依据。     

炎症与动脉粥样硬化关系研究进展

研究表明动脉粥样硬化是一种慢性炎症,在内皮损伤、脂质代谢异常、血流动力学损伤、遗传、感染、物理化学等损伤刺激下,多种炎症因子、免疫机制及相关细胞因子网络交叉样作用于血管壁,形成慢性炎症。炎症反应贯穿于动脉粥样硬化的启动、形成和发展以及不稳定斑块,众多的的炎症标志物为动脉粥样硬化的评估和临床预测提供一条重要途径。抗炎症治疗在动脉粥样硬化的防治中不断取得突破。     

他汀类药物神经保护作用的研究进展

他汀类药物治疗能够显著降低卒中发生率和减轻缺血性脑损伤,通过多种不同的机制发挥神经保护作用,包括稳定动脉粥样硬化斑块、改善内皮功能、减轻炎症反应和再灌注损伤。另外,他汀类药物还能通过阻止β-淀粉样蛋白形成和减少载脂蛋白E分泌而减少痴呆的发生。     

高敏心肌肌钙蛋白对心力衰竭的诊断及预后评估价值

高敏心肌肌钙蛋白升高可见于心肌损伤。心力衰竭过程中多种机制可导致心肌损伤,其常见于急性心力衰竭、慢性心力衰竭急性发作、缺血性心力衰竭,亦可见于非缺血性心力衰竭。高敏心肌肌钙蛋白升高与心力衰竭的死亡率和再住院率密切相关,是评估心力衰竭预后的有力预测因子。     

依达拉奉治疗心血管疾病作用机制的研究进展

依达拉奉对心脏、血管和脑组织的缺血性和炎症损伤具有保护作用,它除了能清除氧自由基外,还具有抗氧化应激、抗凋亡和抗炎的作用,对急性心肌梗死缺血再灌注损伤还具有预防作用。本文就依达拉奉治疗动脉粥样硬化、心肌梗死、高血压、心力衰竭等心血管疾病的作用机制的研究进展综述如下。     

肌钙蛋白自身抗体与心血管疾病

自身免疫在许多心血管疾病的发病机制中起到关键作用,如扩张型心肌病、心肌炎、风湿热和动脉粥样硬化性心脏病。心肌损伤后暴露自身抗原,可能会引发自身免疫反应,一些心脏病患者中可检测到心肌自身抗体,某些健康个体中也可检测到低滴度心肌自身抗体。肌钙蛋白（TnI）是心肌损伤的特异性标志物,在扩张型心肌病及缺血性心肌病患者中可检测到抗-TnI抗体。急性冠脉综合征患者中,抗-TnI抗体的出现可能导致TnI假阴性结果而延误治疗时机。抗-TnI抗体在疾病发病机制中的作用尚未阐明,该文就TnI抗体在心肌病、心肌炎、急性冠脉综合征及心肌梗死后心衰中的作用加以综述。     

Clinical manifestations of coronary aneurysms in the adult as possible sequelae of Kawasaki disease during infancy

Coronary artery aneurysms are rare findings usually diagnosed incidentally at necropsy or at angiography in patients with symptoms of myocardial ischaemia. Even if atherosclerosis is a common cause of coronary aneurysms in the adult, other acquired diseases with inflammatory pathogenesis are associated with coronary artery aneurysms. We present three cases of patients with low probability of coronary artery atherosclerotic disease, due to their age, risk factors profile and history, complaining of chest pain suggestive of myocardial ischaemia and angiographic documentation of one or more coronary aneurysms. In all cases, although no patient had had a previous diagnosis of Kawasaki disease (KD), an unexplained febrile syndrome had occurred in childhood, which is compatible with misdiagnosed episode of KD causing the aneurysmatic lesions. The present reports highlight the potential clinical relevance of previously misdiagnosed KD in patients with ischaemic chest pain, low probability of atherosclerosis and coronary aneurysms.     

The role of carotid atherosclerosis in the distinction between ischaemic and non-ischaemic cardiomyopathy.

AIM: Sometimes ischaemic cardiomyopathy is a result of severe coronary artery disease of an occult course, without typical symptoms or evidence of myocardial infarction. This form of presentation is usually indistinguishable from non-ischaemic dilated cardiomyopathy. Carotid bifurcation atherosclerosis and coronary artery disease have been shown to be strongly associated. We prospectively examined the value of extracranial carotid atherosclerosis in the distinction between ischaemic and non-ischaemic aetiology in patients with clinically unexplained cardiomyopathy. METHODS AND RESULTS: Seventy-eight patients with undetermined dilatation and diffuse impairment of the left ventricular contraction were studied within 28 months. They underwent carotid scan and coronary arteriography. Carotid atherosclerosis was found to be very common in ischaemic and rare in non-ischaemic cardiomyopathy. The presence of at least one abnormal carotid finding (intima-media thickness >1 mm, plaques, severe carotid stenosis) was 96% sensitive and 89% specific for ischaemic cardiomyopathy. CONCLUSION: Carotid scanning may be a useful screening and decision making tool in patients with cardiomyopathy of indecisive cause. Patients with carotid atherosclerosis are likely to suffer from severe coronary artery disease. Coronary angiography and subsequent myocardial viability studies, when indicated, could be considered early during their evaluation. In contrast, a negative carotid scan predicts non-ischaemic cardiomyopathy.     

Rheumatoid disease and ischaemic heart disease: insights from pathophysiology and vascular biology

Rheumatoid disease (RD) is a multisystem inflammatory disorder, which is associated with an increased cardiovascular mortality, thought to be due to ischaemic heart disease (IHD). The precise mechanisms causing increased IHD in RD are unclear. However, there is increasing recognition that atherosclerosis is another chronic inflammatory condition, which shares several pathophysiological features with RD. For example, endothelial damage/dysfunction, platelet activation, hypercoagulability and angiogenesis are well-recognised in both disease processes. Furthermore, RD may influence traditional risk factors such as dyslipidaemia. Although the exact reasons for the increased ischaemic burden are unclear, physicians should place a high priority upon reducing cardiovascular risk in sufferers of RD. This review summarises factors that might contribute to the pathogenesis of IHD in RD. Discussion will focus upon features shared by atherosclerotic and rheumatoid processes, as well as possible interactions between RD and conventional IHD risk factors.     

Silent coronary artery disease in diabetes – a feature of autonomic neuropathy or accelerated atherosclerosis?

Asymptomatic coronary artery disease and myocardial infarctions are common in diabetic subjects. The available clinical and epidemiological data suggest that the increased incidence of asymptomatic myocardial infarctions and coronary artery disease in diabetic patients mainly reflects accelerated coronary atherosclerosis and the proportion of silent disease relative to symptomatic disease or episodes is not increased in diabetes. In spite of the theoretical background, there is no convincing clinical or epidemiological evidence that diabetic autonomic neuropathy plays a major part in the lack of ischaemic pain. This is not surprising because the mechanisms of silent myocardial ischaemia are complex and controversial even without diabetes. [Diabetologia (2001) 44: 259–266]     

Early increase in levels of soluble inter-cellular adhesion molecule-1 (sICAM-1); potential risk factor for the acute coronary syndromes.

BACKGROUND: Studies have shown disparate results in relation to the role of plasma concentrations of cell adhesion molecules in atherosclerosis. Moreover, the differentiation of primary vs secondary alterations of these markers, in response to myocardial injury, has not been clear. We measured specific soluble cell adhesion molecules and inflammatory markers in men admitted acutely with chest pain and compared them to healthy controls. METHODS AND RESULTS: We prospectively studied men (total n=241), admitted acutely with chest pain (7.4+/-9.4 h, 71% within 10 h), unstable angina (n=67), acute myocardial infarction (n=47) and chest pain without ischaemic heart disease (n=45) and compared them with a stratified sample of randomly selected healthy controls (n=82). Soluble intercellular adhesion molecule (sICAM-1), endothelial selectin, vascular cell adhesion molecule, interleukin-6 and C-reactive protein were measured by ELISA and P-selectin expression by flow cytometry. Multiple regression analysis was used to control for the impact of classical risk factors. At baseline ICAM-1, interleukin-6 and C-reactive protein were significantly elevated in patient groups whereas no difference in vascular cell adhesion molecule or endothelial selectin was found. At 3 month follow-up, ICAM-1 level was unchanged in ischaemic heart disease patients. In all groups C-reactive protein and interleukin-6 levels were lower at review. ICAM-1 levels at follow-up were higher in ischaemic heart disease groups (but not in chest pain without ischaemic heart disease) relative to controls and remained so only in the unstable angina group following regression. sICAM-1, interleukin-6 and C-reactive protein strongly correlated with smoking. In the acute phase, ICAM-1 was confounded by smoking following regression and C-reactive protein and interleukin-6 remained significant in both ischaemic heart disease groups after multiple regression. There was no relationship to events which occurred in 23% of ischaemic heart disease patients (further acute myocardial infarction 5.3%, sudden cardiac death 0.9% or recurrent angina 16.7%). CONCLUSION: We found an inflammatory response with higher sICAM-1, interleukin-6 and C-reactive protein in patients presenting soon after developing an acute coronary syndrome. As sICAM-1 was not affected by the acute event this plasma marker may be an important risk factor for the development of the acute coronary syndrome, particularly unstable angina.     

单核-巨噬细胞与缺血性心脏病:心梗引起心梗？

急性冠脉综合征后发生死亡、再梗及卒中等后续不良事件风险增加是缺血性心脏病的研究热点。单核-巨噬细胞广泛参与动脉粥样硬化斑块形成、破裂及心肌缺血损伤、修复。心肌梗死(MI)后交感神经激活,骨髓和脾脏造血作用增强,导致循环中炎性单核细胞激增,改变斑块中巨噬细胞的表型及供应链,从而加速动脉粥样斑块的发展,可能导致再梗或再缺血的发生。本文将对MI如何通过单核-巨噬细胞途径加重动脉粥样硬化进行综述。     

Inflammatory and thrombotic mechanisms in coronary atherosclerosis

Many molecular and cellular mechanisms link inflammation and haemostatic mechanisms. Inflammation, and perhaps chronic infection, may play important roles in the initiation and progression of atherosclerosis. Atherosclerotic lesions are heavily infiltrated by cellular components associated with inflammation (macrophages and T lymphocytes), and acute plaque rupture is also associated with inflammatory components. Several markers of systemic inflammation may predict future cardiovascular events in apparently healthy subjects as well as in patients with chronic and acute syndromes. There may thus be therapeutic potential in modifying the atherosclerotic, vasomotor, and thrombotic components of ischaemic heart disease.     

Endogenous cardioprotective mechanisms - what is it about and how does it work?

Reperfusion therapy is the primary treatment for acute myocardial infarction. Its infarct-limiting effectiveness is, however, limited by so called reperfusion-induced myocardial injury likely related to reperfusion-mediated opening of the mitochondrial permeability transition pore (mPTP). While pharmacologic cardioprotection has proved to effectively reduce infarct size in the experimental models its clinical usefulness is problematic. In this context, a clinical exploitation of endogenous cardioprotective mechanisms, known as ischaemic preconditioning and ischaemic postconditioning, emerges as an attractive therapeutic alternative. This is particularly so because ischaemic pre- and post-conditionig seem to afford cardioprotection by preventing reperfusion-induced deleterious opening of mPTP.     

C-reactive protein and the severity of atherosclerosis in myocardial infarction patients with stable angina pectoris.

BACKGROUND: Recent findings provide evidence for the importance of inflammatory processes in the pathogenesis of atherosclerosis. C-reactive protein was elevated in patients with peripheral artery disease, coronary heart disease and myocardial infarction compared to normal subjects. METHODS: In 1112 male and 299 female survivors of myocardial infarction (mean age +/- SD, men, 50.4 +/- 9.5, women, 56.1 +/- 9.3), we investigated whether plasma C-reactive protein concentration is associated with the severity of coronary heart disease and generalized pre-clinical or clinically manifest arteriopathy. The control group consisted of 326 male and 138 female individuals matched for age without clinical symptoms of coronary disease. The severity of arteriosclerotic changes was determined for the extra-cranial brain-supplying arteries, abdominal aorta, pelvis and leg arteries. In myocardial infarction patients coronary angiography was performed. Laboratory analyses included determination of C-reactive protein, fibrinogen, D-dimer, HDL-cholesterol, LDL-cholesterol and triglycerides. RESULTS: The following ranking of C-reactive protein concentrations was found: controls < or = patients after myocardial infarction without atherosclerosis < or = patients with myocardial infarction and pre-clinical atherosclerosis < or = patients with myocardial infarction and clinically manifest atherosclerosis. Additionally, our data showed a significant association between C-reactive protein concentrations and the angiographically detected degree of coronary heart disease. CONCLUSIONS: As C-reactive protein is a marker of inflammatory processes, our results in patients with clinically manifest and early pre-clinical atherosclerosis support the hypothesis that inflammatory processes in the vessel wall participate in atherogenesis. Moreover, they support the hypothesis of a causal relationship between an acute phase reaction and the pathogenesis of atherosclerosis in coronary arteries and other parts of the arterial vessel system.     

C-reactive protein in atherosclerosis: A causal factor?

Atherosclerosis is considered a to be multifactorial disease driven by inflammatory reactions. The process of inflammation also contributes to the pathogenesis of acute atherothrombotic events. C-reactive protein (CRP) is an acute phase protein and its concentration in serum reflects the inflammatory condition of the patient. Levels of CRP are consistently associated with cardiovascular disease (CVD) and predict myocardial infarctions and stroke. Since CRP is present in the atherosclerotic lesion, it may actively contribute to the progression and/or instability of the atherosclerotic plaque. The role of CRP in inflammation and its causality in atherosclerosis are the subject of many investigations but are not yet fully elucidated. This review focuses on recently identified mechanisms by which CRP may modulate and evolve the process of atherosclerosis. We discuss the function of CRP and review the most recent evidence for an independent role of CRP in the development of atherosclerosis. Many studies suggest such a role, but a number of the described effects may be the result of contamination of the CRP preparations.