单核细胞趋化蛋白-1与心力衰竭的关系研究进展

炎症与心力衰竭的关系是心血管领域的研究热点。单核细胞趋化蛋白-1作为重要的促炎因子之一,与心力衰竭的关系十分密切。现对单核细胞趋化蛋白-1在心力衰竭中的表达、致心力衰竭机制、抗单核细胞趋化蛋白-1与心力衰竭预后等方面进行综述。     

单核细胞趋化蛋白-1在冠心病中的研究

单核细胞趋化蛋白-1(MCP-1)作为重要的促炎因子之一,与CHD关系十分密切。MCP-1趋化并激活单核/巨噬细胞,介导炎症反应。在高血压伴动脉粥样病变的病人中MCP-1过表达,也是动脉粥样硬化形成的独立危险因子。在心肌梗死病人血浆中MCP-1水平明显升高,还可以是长期预测急性冠脉综合征病人死亡和心力衰竭的独立因子。MCP-1基因多态性的不同与CHD的相关性不同,或许与人的不同种族基因分布存在差异有关。     

单核细胞趋化蛋白-1在冠心病中的研究

单核细胞趋化蛋白-1(MCP-1)作为重要的促炎因子之一,与CHD关系十分密切。MCP-1趋化并激活单核/巨噬细胞,介导炎症反应。在高血压伴动脉粥样病变的病人中MCP-1过表达,也是动脉粥样硬化形成的独立危险因子。在心肌梗死病人血浆中MCP-1水平明显升高,还可以是长期预测急性冠脉综合征病人死亡和心力衰竭的独立因子。MCP-1基因多态性的不同与CHD的相关性不同,或许与人的不同种族基因分布存在差异有关。     

氧化型高密度脂蛋白对人单核细胞株THP-1细胞迁移及单核细胞趋化蛋白1含量的影响

为研究氧化型高密度脂蛋白对单核细胞的趋化作用及单核细胞趋化蛋白 1含量的影响 ,进一步探讨氧化型高密度脂蛋白的致动脉粥样硬化机制 ,以一次性密度梯度超速离心法分离人血浆高密度脂蛋白 ,硫酸铜介导法进行氧化修饰 ,单核细胞为培养的人单核细胞株THP 1细胞 ,趋化实验采用改良Boyden趋化室 ,酶联免疫吸附检测法测定单核细胞趋化蛋白 1的含量。结果显示 ,氧化型高密度脂蛋白对THP 1细胞具有明显的趋化作用 ,其蛋白质浓度在 5 0和 10 0mg L时进入膜内的细胞数分别是对照组的 2倍 (P <0 .0 5 )和 3倍 (P <0 .0 1) ;雌二醇可部分抑制氧化型高密度脂蛋白对THP 1细胞的趋化作用。氧化型高密度脂蛋白可促进THP 1细胞单核细胞趋化蛋白 1的释放 ,氧化型高密度脂蛋白组单核细胞趋化蛋白 1的水平 ,约为对照组的 2倍 (P <0 .0 1) ;雌二醇可部分抑制氧化型高密度脂蛋白对THP 1细胞单核细胞趋化蛋白 1释放的促进作用。以上提示 ,氧化型高密度脂蛋白还可能通过促进循环血中单核细胞向血管内膜层迁移和聚集以及单核细胞趋化蛋白 1的释放而促进动脉粥样硬化的发生 ,雌二醇对其具有一定的保护作用     

单核细胞趋化蛋白-1与恶性胸腔积液

单核细胞趋化蛋白-1可促进癌细胞生长、转移及逃避机体免疫破坏,诱导肿瘤新生血管形成,增加血管通透性和参与肿瘤相关炎症反应.本文从恶性胸腔积液的发病机制着手,重点阐述单核细胞趋化蛋白-1在恶性胸腔积液发生、发展中的作用.     

肺癌患者血清单核细胞趋化蛋白-1含量和活性的变化及其意义

目的 探讨肺癌患者血清单核细胞趋化蛋白-1(MCP-1)含量和单核细胞趋化活性(MCA)的变化规律.方法 采用ELISA测定肺癌组和健康对照组血清MCP-1的含量,并以Boyden小室趋化实验测定两组血清MCA.结果 肺癌组血清MCP-1含量明显高于健康对照组(P<0.01),但肺癌组血清MCA却明显低于健康对照组(P<0.01).肺癌组血清MCP-1含量与MCA的相关系数(r=0.39)明显低于健康对照组(r=0.87).结论 肺癌患者存在单核细胞趋化活性不足.     

单核细胞趋化蛋白-1与胰腺炎关系的研究进展

单核细胞趋化蛋白-1(MCP-1)是CC类趋化因子家族中的主要成员之一,对单核细胞、巨噬细胞、淋巴细胞具有很强的趋化活性,在免疫炎症反应、动脉粥样硬化、HIV感染等一系列疾病过程中发挥重要作用。近年来其在胰腺炎的发病和疾病发展中所起的作用越来越受到重视。本文就MCP-1与胰腺炎关系的研究进展作一综述。     

玉葵清对糖基化终产物诱导的人肾系膜细胞趋化因子表达的影响

目的 探讨玉葵清对糖基化终产物（AGEs）诱导的人肾系膜细胞（HRMC）趋化因子表达及其趋化效应的影响. 方法 糖基化牛血清白蛋白（AGE-BSA）和玉葵清干预HRMC. 结果 AGE-BSA组较BSA组HRMC趋化单核细胞数增加,单核细胞趋化蛋白-1（MCP-1）、Fractalkine（FKN）中和抗体组HRMC趋化单核细胞数较AGE-BSA组减少;玉葵清组MCP-1、Fractalkine基因表达、上清中的蛋白含量和趋化单核细胞较BSA组降低（P＜0.05）. 结论 玉葵清减弱AGE-BSA诱导的HRMC趋化因子表达及其趋化效应,可能改善DN肾脏炎症反应.     

单核细胞趋化蛋白-1与糖尿病动脉粥样硬化的关系

糖尿病慢性并发症遍及全身各重要器官,与非糖尿病人群相比,糖尿病人群中心血管疾病患病率升高2～4倍,在血管病变过程中,单核细胞趋化蛋白-1(MCP-1)起了重要作用.MCP-1是细胞因子趋化因子亚家族中的一员,MCP-1在生理情况下呈低水平表达,糖尿病时在高血糖、蛋白非酶糖化产物、血管紧张素Ⅱ、氧化应激、炎症等刺激因素影响下表达明显上调.MCP-1可促使外周血单核细胞向血管内皮细胞黏附、趋化并迁移至内皮下,导致血管平滑肌细胞异常增殖,参与动脉粥样硬化发生的病理过程.本文就糖尿病时MCP-1表达上调的因素、MCP-1促进动脉粥样硬化的机制、干预治疗对MCP-1的影响作一综述,进一步认识MCP-1与糖尿病动脉粥样硬化的关系.     

单核细胞趋化蛋白-1及受体在血管紧张素Ⅱ诱导的血管病变中的作用

在血管紧张素Ⅱ诱导的血管病变中,单核细胞趋化蛋白-1是最重要的化学趋化因子之一。血管紧张素Ⅱ通过一系列分子途径诱导单核细胞趋化蛋白-1的产生,并与其受体CCR2结合,进而引起或加速一系列血管疾病的进程。现就单核细胞趋化蛋白-1及受体CCR2在血管病变中的作用及血管紧张素Ⅱ诱导单核细胞趋化蛋白-1表达的分子途径作一综述。     

Exercise training decreases plasma levels of soluble CD40 ligand and P-selectin in patients with chronic heart failure

BACKGROUND: Inflammation may contribute to the pathogenesis of chronic heart failure. Some reports suggesting that exercise training may have net anti-inflammatory effects in heart failure patients exists, although the results are somewhat conflicting. METHODS: Fifteen patients with mild to moderate chronic heart failure underwent an exercise training program of 20 weeks. They were examined at baseline, at the end of the training period, and 1 year after end of training. RESULTS: Our main findings were as follows: (i) during the training period there was a significant increase in exercise capacity as estimated by the 6-min walk test as well as an improvement in several quality of life parameters, (ii) these changes were accompanied by a marked decrease in plasma levels of soluble CD40 ligand and P-selectin, probably reflecting an attenuated platelet-mediated inflammation, (iii) in contrast, there were no changes in plasma levels of tumor necrosis factor alpha, monocyte chemoattractant protein-1, or vascular cellular adhesion molecule-1 during the training period, (iv) except for an increase in systolic annular velocity there were no changes in echocardiographic variables during the training period, (v) one year after the training, in a period without systematic training, plasma levels of soluble CD40 ligand, and P-selectin had returned to baseline levels along with a nonsignificant reduction in 6-min walk test. CONCLUSION: Our findings suggest a potent downregulatory effect of exercise training on platelet-mediated inflammation in patients with chronic heart failure. Further studies are needed to clarify the clinical significance of these findings.     

Diastolic dysfunction in hypertensive hearts: roles of perivascular inflammation and reactive myocardial fibrosis.

There is increasing evidence that myocardial fibrosis plays a role in the pathogenesis of diastolic dysfunction in hypertensive heart disease. However, it has been difficult to explore the mechanisms of isolated diastolic dysfunction in hypertensive hearts because of the lack of adequate animal models. Recently, we demonstrated that Wistar rats with a suprarenal aortic constriction (AC) can be used as a model of cardiac hypertrophy associated with preserved systolic, but impaired diastolic function without overt congestive heart failure. In this model, acute pressure elevation induces reactive myocardial fibrosis (perivascular fibrosis followed by intermuscular interstitial fibrosis) and myocyte/left ventricular (LV) hypertrophy. Perivascular macrophage infiltration, which is mediated by monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1, exerts a key role in myocardial fibrosis, but not in myocyte/LV hypertrophy. Transforming growth factor (TGF)-beta is crucial for reactive fibrosis in AC rats. MCP-1 function blocking not only inhibits macrophage infiltration and TGF-beta induction but also prevents reactive fibrosis and diastolic dysfunction, without affecting blood pressure, myocyte/LV hypertrophy, or systolic function. Accordingly, a substantial role of inflammation is indicated in myocardial fibrosis and diastolic dysfunction in hypertensive hearts. Currently, the precise mechanisms whereby acute pressure elevation triggers inflammation remain unknown, but it is likely that activation of the tissue angiotensin system is involved in the induction of the inflammatory process.     

Chemokines in myocardial ischemia

Chemokine expression is markedly upregulated in healing myocardial infarcts and may play an important role in regulating leukocyte infiltration and activity and in modulating infarct angiogenesis as well as fibrous tissue deposition. The CC chemokine monocyte chemoattractant protein-1/CCL2 has important effects in infarct healing. Monocyte chemoattractant protein-1 -/- mice exhibit reduced macrophage infiltration and activation, suppressed cytokine synthesis, delayed phagocytotic removal of dead cardiomyocytes, diminished myofibroblast accumulation, and decreased ventricular remodeling after myocardial infarction. Monocyte chemoattractant protein-1 may also play an important role in the development of interstitial fibrosis in ischemic noninfarctive cardiomyopathy. CXC chemokines are also induced in healing infarcts. Interleukin-8/CXCL8 may mediate neutrophil recruitment and activation and may promote neovessel formation, whereas induction of the angiostatic and antifibrotic chemokine interferon-gamma-inducible protein-10/CXCL10 may serve to prevent premature wound angiogenesis and fibrous tissue deposition in the infarct, until the injured myocardium has been cleared from dead cells and debris and a fibrin-rich provisional matrix is formed. Understanding of the role of chemokines in myocardial ischemia may result in novel strategies in the treatment of patients with ischemic heart disease.     

Important role of Rho-kinase in the pathogenesis of cardiovascular inflammation and remodeling induced by long-term blockade of nitric oxide synthesis in rats

Chronic inhibition of endothelial NO synthesis by the administration of N(G)-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular inflammation (monocyte infiltration into coronary vessels and monocyte chemoattractant protein-1 expression) as well as subsequent arteriosclerosis. The small GTPase Rho controls cell adhesion, motility, and proliferation and is activated by several growth factors such as angiotensin II. We investigated the effect of a specific inhibitor of Rho-kinase, Y-27632, in rats treated with L-NAME to determine the role of the Rho/Rho-kinase pathway in the development of arteriosclerosis. We found here increased activity of Rho/Rho-kinase after L-NAME administration and its prevention by angiotensin II type 1 receptor blockade. Hydralazine or lecithinized superoxide dismutase (l-SOD) did not affect Rho/Rho-kinase activity. Co-treatment with Y-27632 did not affect the L-NAME-induced increase in cardiovascular tissue ACE activity or L-NAME-induced decrease in plasma NO concentrations, but did prevent the L-NAME-induced early inflammation and late coronary arteriosclerosis. In addition, Y-27632 prevented the increased gene expression of monocyte chemoattractant protein-1 and transforming growth factor-beta1 as well as cardiac fibrosis and glomerulosclerosis. These findings suggest that increased activity of Rho/Rho-kinase pathway mediated via the angiotensin II type 1 receptor may thus be important in the pathogenesis of early vascular inflammation and late remodeling induced by chronic inhibition of NO synthesis. The beneficial effects of Rho-kinase inhibition are not mediated by restoration of NO production. The Rho-kinase pathway could be a new therapeutic target for treatment of vascular diseases.     

Cross-sectional correlates of serum heat shock protein 70 in the community

BACKGROUND: Recent studies of referral samples suggest that heat shock proteins play a key role in the pathogenesis of high BP and cardiovascular diseases (CVD) including heart failure. It is unclear whether circulating heat shock protein 70 (HSP70) levels are related to CVD risk factors, echocardiographic indexes of left ventricular (LV) remodeling, and prevalent CVD in the population. METHODS: We evaluated the cross-sectional relations of serum HSP70 to established CVD risk factors (including hypertension), markers of oxidative stress (urinary 8-epi-PGF(2alpha)) and inflammation (plasma interleukin-6, C-reactive protein, monocyte chemoattractant protein-1 MCP-1, and soluble intercellular adhesion molecule sICAM-1), echocardiographic LV dimensions and prevalent CVD in 456 Framingham Offspring Study participants (mean age 61 years, 42% women). RESULTS: In multivariable analyses, serum HSP70 was not associated with age, sex, vascular risk factors (including hypertension), echocardiographic LV mass or prevalent CVD. Also, serum HSP70 was not related to any of the biomarkers evaluated (p> or = 0.10 for all). CONCLUSIONS: In our community-based sample, serum HSP70 was similar in men and women, and not significantly related to traditional or novel risk factors, to LV mass or to prevalent CVD. Our data suggest that blood levels may not adequately reflect the important role of heat shock proteins in prevalent CVD.     

Targeted cardiac expression of soluble Fas prevents the development of heart failure in mice with cardiac-specific expression of MCP-1

Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in initiating coronary heart disease by recruiting monocytes/macrophages to the vessel wall. Transgenic mice with cardiac-specific expression of MCP-1 manifest cardiac inflammation and develop heart failure. The pathways mediating the detrimental effects of MCP-1 expression have not been defined. We postulate that the Fas ligand (FasL) derived from the infiltrating mononuclear cells causes death of cardiac cells resulting in the development of heart failure. Here, we tested this hypothesis by determining whether inhibition of FasL function through cardiac-specific expression of soluble Fas (sFas) would rescue the MCP-1 transgenic mice from developing heart failure. We generated mice with cardiac-specific expression of sFas and double homozygous transgenic mice that express both MCP-1 and sFas. Cardiac-specific expression of sFas in MCP mice, in fact, inhibited apoptosis of infiltrating mononuclear cells, normalized circulating C-reactive protein (CRP) levels, and prevented macrophage activation as well as production of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 in the hearts. sFas expression resulted in restoration of cardiac structure, preservation of cardiac function, and a significant prolongation of survival of MCP mice. These results demonstrate that FasL released from infiltrating mononuclear cells plays a critical role in the detrimental effects of MCP-1 expression, and suggest that Fas/FasL signaling represents a novel therapeutic target for heart failure.     

Decreased Expression of Monocyte Chemoattractant Protein-1 Predicts Poor Prognosis Following Curative Resection of Colorectal Cancer

Purpose  The significance of monocyte chemoattractant protein-1 in colorectal cancer is not well understood. The aim of this study was to investigate the significance of monocyte chemoattractant protein-1 expression in colorectal cancer patients undergoing potentially curative surgery. Methods  We studied 101 colorectal cancer patients who underwent potentially curative surgery. The concentration of monocyte chemoattractant protein-1 in the tumor and normal mucosa were measured. The expression of monocyte chemoattractant protein-1 was also evaluated immunohistochemically. Results  The tissue concentration of monocyte chemoattractant protein-1 in the tumor was significantly higher than that in the normal mucosa. The decreased monocyte chemoattractant protein-1 cancer/normal ratio was associated with lymph node involvement and could predict poor prognosis. On univariate analysis, the decreased monocyte chemoattractant protein-1 ratio, carcinoembryonic antigen levels, and serosal invasion were the significant factors for poor prognosis. Multivariate analysis showed that monocyte chemoattractant protein-1 ratio was the only independent risk factor predictive of a poor prognosis. Immunohistochemically, monocyte chemoattractant protein-1 was expressed in the cytoplasm. Conclusion  The decreased monocyte chemoattractant protein-1 ratio was an independent factor predicting poor prognosis in patients undergoing potentially curative surgery. Monocyte chemoattractant protein-1 deficiency may present a new therapeutic approach for colorectal cancer.