C反应蛋白与动脉粥样硬化

C反应蛋白（C-reactiveprotein,CRP）是人类非特异性急性期蛋白,是判断组织损伤和炎症反应的敏感指标之一。CRP的表达水平与动脉粥样硬化（atherosclerosis,AS）和心血管疾病的发生具有冠著的相关性。但是关于CRP是否是AS的独立危险因素并参与AS的发病机制,目前尚存在很大争议。新近的研究发现,CRP与某些特定的配体结合后,五聚体结构CRP可分离形成单体结构CRP。这一发现为研究CRP蛋白与AS的相互关系提供了新的线索,对CRP及其单体结构的深入研究,将有可能帮助人们找到治疗心血管疾病的有效方法。就炎性反应标志物CRP及其单体（monomeric CRP,mCRP）与动脉粥样硬化的相关研究进展进行综述,以探讨分析CRP在AS中的作用。     

巨噬细胞因子daintain激活血液炎症反应

Daintain是我们鉴定并命名的巨噬细胞炎症因子。多个小组的研究表明daintain与炎症密切相关,但截至目前尚缺乏两者关联的直接证据。本实验研究了daintain对昆明鼠血液C反应蛋白(C-reactive protein,CRP)和纤维蛋白原的影响,结果表明daintain促进血液CRP的增高,激活纤维蛋白原,此外还观察到daintain增加了血液粘度并加速血液凝固。这些结果提示daintain可直接激发血管炎症反应,可能促进心血管疾病的发生。     

C反应蛋白--天然防御蛋白研究进展

C反应蛋白(C-reactive protein,CRP)是急性时相蛋白中最突出的代表,在机体遭受损伤后,它在体内会急速上升,因而被认为是感染和炎症的早期指示灯。CRP是属于古老并高度保守的“pentraxin”蛋白家族,是由5个非共价联合的单体(protomers)组成。CRP具有多种生理功能,能与多种糖蛋白和磷酸酯类结合,能对补体系统进行调节,对机体具有调理作用,对细胞凋亡有一定的影响等等。CRP检测技术的发展使人们对CRP的结构和生理功能越来越了解,更认识到其在临床医学中的巨大应用价值。     

戊型肝炎病毒感染激活补体系统

为了探究补体系统与戊型肝炎病毒复制的相关性,分别在HEV感染的A549细胞和BALB/c小鼠中检测C3aR、CD55和CD59蛋白的表达.利用RT-qPCR定量检测细胞和组织中补体的表达,采用免疫组化法检测HEV感染BALB/c小鼠中补体CD59及C5b-9的表达,ELISA检测补体相关炎症因子的变化.HEV感染可以激活补体蛋白C3aR、C5b-9、CD55和CD59的表达,引起补体蛋白相关炎症因子IL-10表达水平下降,IL-12和TNF-α的表达水平的上升,从而导致机体的炎症反应,加剧组织损伤.HEV感染激活补体系统并参与早期的抗病毒反应,HEV感染对补体的持续激活导致炎症因子过度表达,加重机体损伤.     

C-反应蛋白——关联心血管疾病与炎症的重要分子

炎症在心血管疾病（cardiovascular disease,CVD）的各个阶段中均发挥着重要作用。C-反应蛋白（C-reactive protein,CRP）是一种典型的人类急性期蛋白,由5个相同的亚基构成,在临床上被广泛用作炎症的非特异性标识物。近年的研究显示,CRP不仅是CVD发病风险的灵敏标识,而且直接参与调控与CVD相关的炎症过程。基于对已有研究发现的回顾和分析,文章指出CRP的单体形式（monomeric CRP, mCRP）是调控局部炎症过程的主要CRP异构体。     

硒蛋白S基因多态性研究进展

硒蛋白S（selenoprotein S,SELS）是一种在内质网和细胞膜潴留的硒蛋白,是一种新发现的炎症负调控因子,可以保护细胞免受氧化损伤,参与炎症和免疫反应。SELS基因多态性与肿瘤、心血管疾病、缺血性中风和先兆子痫等疾病的发生风险相关。简要介绍SELS的生物学功能,并对近年来SELS基因多态性与疾病易感性的研究进行回顾。     

炎症因子表达水平与重症急性胰腺炎预后及肠道屏障损伤的相关性

摘要 目的：探讨白细胞介素-6（IL-6）、降钙素原（PCT）、C反应蛋白（CRP）相关炎症因子表达水平对重症急性胰腺炎（SAP）预后的预测价值,并分析不同炎症因子表达与肠道屏障损伤的相关性。方法：选取我院2019年8月到2022年8月收治的60例SAP患者为研究对象,对所有患者进行28 d随访,将28 d内死亡的20例患者分为死亡组,将其余40例患者分为存活组,对比两组患者临床一般情况与IL-6、PCT、CRP相关炎症因子表达水平,并分析SAP预后影响的独立危险因素。随后将所有患者依照肠道屏障损伤情况进行分组,分为肠道屏障损伤组（n=42）与非肠道损伤组（n=18）,对比两组患者IL-6、PCT、CRP表达水平,分析炎症因子表达水平与肠道屏障损伤的相关性,并绘制各指标诊断SAP肠道屏障损伤的ROC曲线,分析其预测肠道屏障损伤的灵敏度与特异度。结果：存活组与死亡组患者胰腺坏死、APACHEⅡ评分、发生器官衰竭情况与IL-6、PCT、CRP表达水平对比差异显著（P＜0.05）;PCT、CRP、APACHEⅡ评分为重症胰腺炎患者的预后不良影响因素（P＜0.05）;肠道屏障损伤组患者IL-6、PCT、CRP表达水平明显高于非肠道屏障损伤组（P＜0.05）;Spearman相关分析结果显示：IL-6、PCT、CRP与肠道屏障损伤呈正相关（P＜0.05）;ROC曲线分析显示：曲线下面积（AUC）从低到高依次为IL-6 (0.631)、CRP（0.667）、PCT（0.671）、联合诊断（0.852）。血清IL-6、PCT、CRP的联合诊断的灵敏度与特异度明显高于血清IL-6、PCT、CRP单一诊断（P＜0.05）。结论：IL-6、PCT、CRP相关炎症因子表达水平可预测SAP患者预后情况,IL-6、PCT、CRP与SAP肠道屏障损伤呈正相关,且三者联合对SAP肠道屏障损伤的诊断具有重要价值。     

JCEM:阿司匹林或能增加有流产史女性的成功怀孕几率

正日前,一项刊登在国际杂志the Journal of Clinical Endocrinology and Metabolism上的研究报告中,来自美国国立卫生研究院的研究人员通过研究发现,每日低剂量的阿司匹林或能有效帮助曾经流产过的女性成功怀孕妊娠。这些因阿司匹林获益的女性机体中含有较高水平的C反应蛋白(CRP),这种蛋白是血液中能够指示机体整个系统炎症的特殊蛋白,而阿司匹林被认为能够有效中和这种炎症反应。研究人员对来自"阿司匹林对怀孕和生育影响试验"(EAGe R)计划中的原始数据进行分析,这项计划的     

炎症中出现的C-反应蛋白是高血压症的预兆

在炎症中出现的一种蛋白质可能是高血压的危险信号,研究者在首次大规模试验中报道了炎症与高血压的关系.该蛋白质称为C 反应蛋白(CRP) ,已知在心脏病与高血压中出现.以此为据,有些医生已开始常规测试CRP在血中浓度升高的情况.许多研究指出,低度的炎症引起血管损伤.当CRP对炎症或心脏病的作用远未搞清之时,高血压便成为心脏病及卒中的极佳的可识别的危险信号.研究者检查了2 0 5 2 5位妇女的血样,这些血样是早在2 0世纪90年代为“妇女生卫研究项目”中部分广范围研究而捐献的.进入该项研究的妇女都在4 5岁以上,无高血压、卒中或癌症病史,…     

同型半胱氨酸与超敏c反应蛋白在妊娠期高血压疾病中的研究进展

妊娠期高血压疾病是妊娠期特有的疾病,早期诊断对预后至关重要。妊娠期高血压疾病发病机制之一为血管内皮损伤,血浆中Hcy浓度升高会导致血管内皮损伤,血管内皮细胞功能失调常刺激超敏C反应蛋白（hs—cRP）的产生,而升高的hs—CRP可能导致血压上升。因此高血压和慢性炎症相互促进从而导致和加重了高血压。近年来血浆同型半胱氨酸（Hcy）、超敏C反应蛋白（hs—cRP）水平的升高与妊娠期高血压疾病的关系成为新的研究热点。本文将同型半胱氨酸、超敏C反应蛋白与妊娠期高血压疾病中的关系综述如下。     

No reduction of atherosclerosis in C-reactive protein (CRP)-deficient mice

C-reactive protein (CRP), a phylogenetically highly conserved plasma protein, is the classical acute phase reactant in humans. Upon infection, inflammation, or tissue damage, its plasma level can rise within hours >1000-fold, providing an early, nonspecific disease indicator of prime clinical importance. In recent years, another aspect of CRP expression has attracted much scientific and public attention. Apart from transient, acute phase-associated spikes in plasma concentration, highly sensitive measurements have revealed stable interindividual differences of baseline CRP values in healthy persons. Strikingly, even modest elevations in stable baseline CRP plasma levels have been found to correlate with a significantly increased risk of future cardiovascular disease. These observations have triggered intense controversies about potential atherosclerosis-promoting properties of CRP. To directly assess potential effects of CRP on atherogenesis, we have generated CRP-deficient mice via gene targeting and introduced the inactivated allele into atherosclerosis-susceptible ApoE(-/-) and LDLR(-/-) mice, two well established mouse models of atherogenesis. Morphometric analyses of atherosclerotic plaques in CRP-deficient animals revealed equivalent or increased atherosclerotic lesions compared with controls, an experimental result, which does not support a proatherogenic role of CRP. In fact, our data suggest that mouse CRP may even mediate atheroprotective effects, adding a cautionary note to the idea of targeting CRP as therapeutic intervention against progressive cardiovascular disease.     

C-reactive Protein

C-reactive protein (CRP) is a phylogenetically highly conserved plasma protein, with homologs in vertebrates and many invertebrates, that participates in the systemic response to inflammation. Its plasma concentration increases during inflammatory states, a characteristic that has long been employed for clinical purposes. CRP is a pattern recognition molecule, binding to specific molecular configurations that are typically exposed during cell death or found on the surfaces of pathogens. Its rapid increase in synthesis within hours after tissue injury or infection suggests that it contributes to host defense and that it is part of the innate immune response. Recently, an association between minor CRP elevation and future major cardiovascular events has been recognized, leading to the recommendation by the Centers for Disease Control and the American Heart Association that patients at intermediate risk of coronary heart disease might benefit from measurement of CRP. This review will largely focus on our current understanding of the structure of CRP, its ligands, the effector molecules with which it interacts, and its apparent functions.     

Thematic review series: The Immune System and Atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease?

In humans, a chronically increased circulating level of C-reactive protein (CRP), a positive acute-phase reactant, is an independent risk factor for cardiovascular disease. This observation has led to considerable interest in the role of inflammatory proteins in atherosclerosis. In this review, after discussing CRP, we focus on the potential role in the pathogenesis of human vascular disease of inflammation-induced proteins that are carried by lipoproteins. Serum amyloid A (SAA) is transported predominantly on HDL, and levels of this protein increase markedly during acute and chronic inflammation in both animals and humans. Increased SAA levels predict the risk of cardiovascular disease in humans. Recent animal studies support the proposal that SAA plays a role in atherogenesis. Evidence is accruing that secretory phospholipase A(2), an HDL-associated protein, and platelet-activating factor acetylhydrolase, a protein associated predominantly with LDL in humans and HDL in mice, might also play roles both as markers and mediators of human atherosclerosis. In contrast to positive acute-phase proteins, which increase in abundance during inflammation, negative acute-phase proteins have received less attention. Apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, decreases during inflammation. Recent studies also indicate that HDL is oxidized by myeloperoxidase in patients with established atherosclerosis. These alterations may limit the ability of apoA-I to participate in reverse cholesterol transport. Paraoxonase-1 (PON1), another HDL-associated protein, also decreases during inflammation. PON1 is atheroprotective in animal models of hypercholesterolemia. Controversy over its utility as a marker of human atherosclerosis may reflect the fact that enzyme activity rather than blood level (or genotype) is the major determinant of cardiovascular risk. Thus, multiple lipoprotein-associated proteins that change in concentration during acute and chronic inflammation may serve as markers of cardiovascular disease. In future studies, it will be important to determine whether these proteins play a causal role in atherogenesis.     

Systemic inflammation and mortality in chronic obstructive pulmonary disease

Cardiovascular diseases and cancer (especially lung cancer) are leading causes of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Some have implicated systemic inflammation, which is commonly observed in COPD, as the potential mechanistic bridge between COPD and these disorders. This concept has been supported by animal studies especially in rabbits, which have clearly demonstrated the effect of local lung inflammation on systemic inflammation and on the progression of atherosclerosis and by cross-sectional population-based studies, which have shown a significant relationship between systemic inflammation, as measured by circulating C-reactive protein (CRP) and the risk of cardiovascular diseases in COPD patients. These data have been further extended by a recent study that has elucidated the temporal nature of the relationship between systemic inflammation and the risk of cardiovascular events and cancer in COPD patients. This study showed that baseline CRP levels predicted the incidence of cardiovascular events and cancer-specific mortality over 7 to 8 years of follow-up. CRP levels also predicted all-cause mortality. Collectively, these data indicate that systemic inflammation may play an important role in mediating the extra-pulmonary complications of COPD. Systemic inflammation may contribute substantially to the overall morbidity and mortality of COPD patients.     

Chronic administration of NMU into the paraventricular nucleus stimulates the HPA axis but does not influence food intake or body weight

C-reactive protein (CRP), a predictor of future cardiovascular diseases, has been reported to damage the vascular wall by inducing endothelial dysfunction and inflammation. This proatherogenic CRP was speculated to have a role in attenuating angiogenic functions of human endothelial progenitor cells (EPCs), possibly impairing vascular regeneration and increasing cardiovascular vulnerability to ischemic injury. Herein, we investigated the direct effect of CRP on angiogenic activity and gene expression in human EPCs. Incubation of EPCs with human recombinant CRP significantly inhibited EPC migration in response to vascular endothelial growth factor, possibly by decreasing the expression of endothelial nitric oxide synthase and subsequent nitric oxide production. In addition, CRP-treated EPCs showed the reduced adhesiveness onto an endothelial cell monolayer. When assayed for the gene expression of arteriogenic chemo-cytokines, CRP substantially decreased their expression levels in EPC, in part due to the upregulation of suppressors of cytokine signaling proteins. These results suggest that CRP directly attenuates the angiogenic and possibly arteriogenic functions of EPCs. This CRP-induced EPC dysfunction may impair the vascular regenerative capacity of EPCs, thereby leading to increased risk of cardiovascular diseases.     

C-reactive protein as a risk factor versus risk marker

PURPOSE OF REVIEW: C-reactive protein (CRP) is consistently associated with cardiovascular disease in prospective and cross-sectional clinical and epidemiological studies. Inflammation is an important mechanism in cardiovascular disease, and the plasma level of CRP is considered to reflect the inflammatory condition of the patient and/or the vessel wall. In addition, there are also a number of indications for a causal role of CRP in cardiovascular disease. RECENT FINDINGS: A number of new publications show potential causal effects of CRP on cardiovascular disease, and evidence from human-CRP transgenic animals also indicates a causal contribution of CRP to cardiovascular disease. On the other hand, a new large prospective study and an updated meta-analysis indicate that the contribution of CRP to cardiovascular disease is less impressive than reported earlier (odds ratio, 1.58; 95% confidence interval, 1.48-1.68). SUMMARY: We review here the most recent evidence on mechanisms by which CRP is involved as a causal factor in the precipitation of cardiovascular disease. Evidence for such a role is accumulating.     

Atherothrombosis: role of tissue factor; link between diabetes, obesity and inflammation

Atherothrombotic vascular disease is a complex disorder in which inflammation and coagulation play a pivotal role. Rupture of high-risk, vulnerable plaques with the subsequent tissue factor (TF) exposure is responsible for coronary thrombosis, the main cause of unstable angina, acute myocardial infarction, and sudden cardiac death. Tissue factor (TF), the key initiator of coagulation is an important modulator of inflammation. TF is widely expressed in atherosclerotic plaques and found in macrophages, smooth muscle cells, extracellular matrix and acellular lipid-rich core. TF expression can be induced by various stimulants such as C-reactive protein, oxLDL, hyperglycemia and adipocytokines. The blood-born TF encrypted on the circulating microparticles derived from vascular cells is a marker of vascular injury and a source of procoagulant activity. Another form of TF, called alternatively spliced has been recently identified in human and murine. It is soluble, circulates in plasma and initiates coagulation and thrombus propagation. Evidence indicates that elevated levels of blood-borne or circulating TF has been associated with metabolic syndrome, type 2 diabetes and cardiovascular risk factors and is a candidate biomarker for future cardiovascular events. Therapeutic strategies have been developed to specifically interfere with TF activity in the treatment of cardiovascular disease.     

Melanocortin receptor expression is associated with reduced CRP in response to resistance training

The existing paradigm of exercise-induced decreases in chronic inflammation focuses on the expression of inflammatory receptors on systemic monocytes in response to exercise training, with the role of anti-inflammatory receptors largely ignored. Our recent preliminary studies indicate that the anti-inflammatory melanocortin receptors (MCRs) may play a role in modulating exercise-induced decreases in chronic inflammation. Here, we present a study designed to determine the effect of intense, resistance exercise training on systemic monocyte MCR expression. Because low-grade chronic inflammation is associated with elevated cardiometabolic risk in healthy populations and exercise decreases chronic inflammation, we investigated the associations between systemic monocyte cell surface expression of MCRs and inflammatory markers as a possible mechanism for the beneficial anti-inflammatory effects of resistance training. To this end, the present study includes 40 adults (aged 19-27 yr) and implements a 12-wk periodized, intensive resistance training intervention. Melanocortin 1 and 3 receptor expression on systemic monocytes and inflammatory markers, including C-reactive protein (CRP), interleukin (IL)-6, IL-1β, and IL-10, were measured before and after the intervention. Resistance training significantly altered MCR systemic monocyte cell surface expression, had no chronic effects on IL-6, IL-1β, or IL-10 expression, but significantly decreased CRP levels from a moderate to a low cardiovascular disease risk category. More specifically, decreased melanocortin 3 receptor expression significantly correlated with decreased CRP, independent of changes in adiposity. These data suggest that the observed responses in MCR expression and decreases in cardiovascular disease risk in response to resistance training represent an important anti-inflammatory mechanism in regulating exercise-induced decreases in chronic inflammation that occur independent of chronic changes in systemic cytokines.