同型半胱氨酸、炎症与动脉粥样硬化

高同型半胱氨酸血症是动脉粥样硬化形成的一种独立危险因素。动脉粥样硬化是一种慢性炎症过程,从炎症角度出发研究同型半胱氨酸与动脉粥样硬化的关系也得到了人们的关注。现就炎症在同型半胱氨酸致动脉粥样硬化的作用及其机制方面的研究进展作一综述。     

Antioxidants,statins, and atherosclerosis

Research into the oxidation of lipoproteins has yielded many new insights into the pathogenesis of atherosclerosis. However, despite lipoprotein oxidation's biologically plausible role in atherogenesis, several studies have reported inconsistent effects of antioxidants on clinical coronary end points, in sharp contrast with the studies of lipid modification with the 3-hydroxy-3-methylglutaryl coenzyme A inhibitors, or statins. There appears to be little support for the use of antioxidants in coronary prevention. However, the picture remains incomplete. What are the limitations of available antioxidant studies and the agents used? Until the picture can be clarified, lipid modification with strategies proved to reduce the risk for coronary events, such as statins or dietary changes in the style of the Mediterranean diet, should be better implemented in clinical practice.     

Aging, telomeres, and atherosclerosis

Although the level and pace of population aging display high geographical variability, virtually all countries have been experiencing growth in their elderly population, particularly in developed nations. Because aging is a major risk factor for atherosclerosis and associated disease, it is of up most importance to unravel the molecular mechanisms involved in vascular aging. Telomeres are specialized DNA-protein structures located at the ends of eukaryotic chromosomes whose length is progressively reduced in most somatic cells during aging. It is accepted that telomere exhaustion contributes to organismal ageing at least by impairing cell proliferation and viability. An emerging question is whether telomere erosion contributes to atherosclerosis. Here we discuss recent advances on the molecular control of telomere length in vascular cells, as well as animal and human studies that address the role of telomeres in vascular pathobiology. Although the interrelationships between telomere length and cardiovascular disease appear obvious, a chief question that remains unanswered is whether telomere ablation is cause of vascular injury or a surrogate phenomenon.     

Macrophages, inflammation, and atherosclerosis

The macrophage plays a diverse array of roles in atherogenesis and lipoprotein metabolism. The macrophage functions as a scavenger cell, an immune mediator cell, and as a source of chemotactic molecules and cytokines. Chemokines have been implicated in promoting migration of monocytes into the arterial intima. Monocyte chemoattractant protein-1 (MCP-1) attracts monocytes bearing the chemokine receptor CCR-2. Macrophage expression of cyclooxygenase-2, a key enzyme in inflammation, promotes atherosclerotic lesion formation in low-density lipoprotein receptor (LDLR)-deficient mice. In the arterial intima, monocytes differentiate into macrophages, which accumulate cholesterol esters to form lipid-laden foam cells. Foam cell formation can be viewed as an imbalance in cholesterol homeostasis. The uptake of atherogenic lipoproteins is mediated by scavenger receptors, including SR-A and CD36. In the macrophage, ACAT-1 is responsible for esterifying free cholesterol with fatty acids to form cholesterol esters. Surprisingly, deficiency of macrophage ACAT-1 promotes atherosclerosis in LDLR-deficient mice. A number of proteins have been implicated in the process of promoting the efflux of free cholesterol from the macrophage, including apoE, ABCA1, and SRB-1. Macrophage-derived foam cells express the adipocyte fatty acid-binding protein (FABP), aP2, a cytoplasmic FABP that plays an important role in regulating systemic insulin resistance in the setting of obesity. ApoE-deficient mice null for macrophage aP2 expression develop significantly less atherosclerosis than controls wild type for macrophage aP2 expression. These results demonstrate a significant role for macrophage aP2 in the formation of atherosclerotic lesions independent of its role in systemic glucose and lipid metabolism. Furthermore, macrophages deficient in aP2 display alterations in inflammatory cytokine production. Through its distinct actions in adipocytes and macrophages, aP2 links features of the metabolic syndrome including insulin resistance, obesity, inflammation, and atherosclerosis.     

Aging, atherosclerosis, and IGF-1

Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces atherosclerosis burden and improves features of atherosclerotic plaque stability in animal models. Potential mechanisms for this atheroprotective effect include IGF-1-induced reduction in oxidative stress, cell apoptosis, proinflammatory signaling, and endothelial dysfunction. Aging is associated with increased vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert salutary effects on vascular aging processes. In this review, we will provide a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging.     

Inflammation, insulin resistance, and atherosclerosis

Until recently, atherosclerosis was thought to be a passive process of lipid deposition in the arterial wall, followed by progressive occlusion of the lumen, and finally plaque rupture and thrombosis. Recent data suggest the contrary-atherosclerosis is a dynamic process developing over many years, characterized by active uptake of lipids and smooth muscle proliferation, "molding" of plaque, and subject to the influence of many environmental and genetic factors. Central to these processes, both at initiation and propagation, are factors associated with inflammation. Insulin resistance (IR), the underlying cause of type 2 diabetes mellitus (DM), is also associated with elevated levels of inflammatory factors, such as C reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and fibrinogen. Recent studies indicate that these same factors precede and predict DM. These findings have led to the notion that the strong association of IR/DM with cardiovascular disease (CVD) may be through inflammation pathways. In this article, we review what is known about the association of inflammation with IR and atherosclerosis. We show that many of the same inflammatory factors associated with IR are present in atherosclerosis. We also discuss the underlying determinants of inflammation in these conditions.     

颈动脉粥样硬化与冠状动脉狭窄程度关系的研究

目的:探讨颈动脉粥样硬化(CA S)与冠状动脉粥样硬化(CAA S)的影响因素及二者的关系。方法:202例患者根据冠状动脉造影结果分为非冠心病组(NCHD组,54例,冠状动脉直径狭窄<50%);冠心病组(CHD组,148例,至少一支冠状动脉直径狭窄≥50%)。冠心病组又按其血管病变支数分为三个亚组:单支病变组(30例)、双支病变组(42例)、多支病变组(76例)。采用颈动脉超声检测双侧颈总动脉内-中膜厚度、斑块,与冠状动脉造影结果进行对比研究,比较各组之间二者的关系,分析CA S与CAA S的影响因素。结果:①高血压、低密度脂蛋白与冠状动脉病变支数呈正相关(P<0.05),低密度脂蛋白与颈动脉病变分级呈正相关(P<0.05);②与NCHD组比较,CHD组患者颈动脉内膜增厚率和斑块形成率增高(P<0.05);CHD组各亚组之间比较,多支病变组患者颈动脉斑块形成率、多发斑块发生率高于单支组和双支组(P均<0.05);③颈动脉粥样斑块中软斑和混合斑比例:CHD组的高于NCHD组的(P<0.05);CHD组中多支组高于单支组和双支组(P<0.05);④CAA S的冠状动脉病变积分(CSS)与CA S的颈动脉粥样硬化积分(A S)呈正相关(r=0.61,P<0.05)。结论:①高血压、低密度脂蛋白是动脉粥样硬化的危险因素;②冠状动脉粥样硬化和颈动脉粥样硬化密切相关;③CHD组患者颈动脉动脉硬化病变甚于NCHD组患者;而CHD多支病变组患者的又甚于单支病变组和双支病变组。     

高脂血症、单核细胞亚型与动脉粥样硬化

单核细胞是天然免疫的重要组成部分,在血管炎症和动脉粥样硬化(As)中发挥重要作用。高脂血症可加速心血管疾病,尤其是As的进展。高脂血症时,循环单核细胞能吸收脂质,形成泡沫状单核细胞,改变表型,可能有助于动脉粥样硬化的发展。长期以来,单核细胞及其不同亚型对高脂血症的响应和对As的作用一直是人们研究的热点。本文探讨了人和小鼠的单核细胞亚型特点,高脂血症对单核细胞的影响,以及单核细胞对As的作用等,重点介绍了单核细胞通过脂质吞噬、泡沫细胞形成、巡逻以及迁移入斑块等途径影响As进程的研究进展。     

Dietary fiber, lipids and atherosclerosis

Dietary fiber has important hypocholesterolemic effects and may reduce risk for coronary artery disease. Careful clinical studies indicate that foods such as oat bran or beans, rich in water-soluble fiber, can decrease serum total cholesterol by 19% while decreasing serum low density lipoprotein cholesterol by 22%. Food supplements rich in soluble fiber such as psyllium mucilloid are well tolerated and may lower serum cholesterol by 15%. Thus, high fiber foods or soluble fiber food supplements may decrease serum cholesterol by 15% to 19% and decrease estimated risk for coronary heart disease by greater than 30%.     

SLE, atherosclerosis and cardiovascular disease

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.     

Lipids, lipoproteins and atherosclerosis]

Cardiovascular diseases are the number one cause of death in France: 36.4%. Abnormalities of the metabolism of lipoproteins constitute the major predisposing factor for the development and progression of arterial lesions. These abnormalities are very often genetically linked and their expression is influenced by environmental factors (nutrition, smoking ...). The prevention of cardiovascular diseases is of prime importance and the detection of atherosclerosis risk makes up one of the essential steps to this approach. Detection must be realised as early as possible, for in the cases of metabolic abnormalities, the pathogenicity of the process evolves slowly, without showing outward clinical signs and leads to major long-term damage: myocardial infarction in particular. Measuring total cholesterol and total triglycerides are insufficient, particularly when the values are not extreme, to evaluate atherosclerosis risk; these measurements must be complimented by these of the lipoproteins. Current research allows earlier and more precise biological tests of coronary risk to be envisaged.