Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation

Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF.     

The metabolic syndrome and insulin resistance: relationship to haemostatic and inflammatory markers in older non-diabetic men

AIMS: We have examined the cross-sectional relationship between insulin resistance, the metabolic syndrome and haemostatic and inflammatory markers. METHODS AND RESULTS: We carried out the study in 2722 non-diabetic men aged 60-79 years with no history of coronary heart disease or stroke and who were not on warfarin treatment, drawn from general practices in 24 British towns. Insulin resistance (HOMA) was significantly associated with increased inflammatory markers (C-reactive protein (CRP), white cell count), coagulation factors VII-IX, von Willebrand factor (VWF) and tissue plasminogen activator (t-PA) antigens (markers of endothelial dysfunction) and blood viscosity after adjustment for age, smoking, physical activity, alcohol intake and waist circumference. Relationships with fibrinogen and fibrin D-dimer were weak. The relationship between HOMA and CRP was abolished after adjustment for t-PA. The prevalence of the metabolic syndrome was similar using World Health Organization (WHO) and National Cholesterol Education Program definitions (26.7% and 27.0%) but associations between the metabolic syndrome and increased haemostatic markers, particularly for raised factor VIII and VWF were stronger using WHO criteria. CONCLUSION: Insulin resistance and the metabolic syndrome showed significant associations with markers of haemostasis and inflammation, which may be relevant to their associations with cardiovascular disease.     

Abnormal soluble CD40 ligand and C-reactive protein concentrations in hypertension: relationship to indices of angiogenesis

BACKGROUND: Abnormal inflammation, platelets and angiogenesis are involved in the pathophysiology of cardiovascular disease (CVD). OBJECTIVE: To test the hypothesis that concentrations of high sensitive C-reactive protein (CRP, an index of inflammation) and soluble CD40 ligand (sCD40L, an index of platelet activation) would be abnormal in hypertension, and in turn, be related to plasma indices of angiogenesis, the angiopoietins-1 and -2, and vascular endothelial growth factor (VEGF), in addition to the presence or absence of CVD. METHODS: Using a cross-sectional approach, we measured plasma concentrations of CRP, sCD40L, VEGF, and angiopoietins-1 and -2 in 147 patients with hypertension (85 with a history of CVD event/s, 62 CVD event-free) and 68 age- and sex-matched healthy controls. RESULTS: Concentrations of sCD40L (P = 0.039), CRP (P < 0.001), angiopoietin-1 (P < 0.001), angiopoietin-2 (P = 0.003) and VEGF (P < 0.001) were all greater amongst hypertensive patients than in controls. There were no significant differences in sCD40L and VEGF concentrations between hypertensive individuals with and without CVD events, but CRP and angiopoietin-1 concentrations were significantly greater amongst those with CVD events. On multiple regression analysis, sCD40L was associated with angiopoietin-2 (P = 0.01) and VEGF (P = 0.007) in hypertensive individuals, but no such associations were found within the healthy control group. CONCLUSION: In patients with hypertension, sCD40L was associated with increased circulating markers of abnormal angiogenesis (angiopoietin-2, VEGF). The interaction between sCD40L and angiogenesis may contribute to the pathophysiology of CVD in hypertension.     

Levels of angiogenic factors in patients with multiple myeloma correlate with treatment response

Angiogenesis plays a significant role in the pathogenesis of multiple myeloma (MM). We have measured concentrations of angiogenesis activators, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and hepatocyte growth factor (HGF), and inhibitors, including endostatin, thrombospondin-1 (TSP-1), and angiostatin in the peripheral and bone marrow blood of MM patients at diagnosis and after high-dose chemotherapy. We have analyzed 96 patients with secretory MM. Serial measurements of angiogenesis factors/inhibitors were analyzed in the plasma by subgroups based on the best treatment response. Concentrations of angiogenic factors were determined in the peripheral blood and bone marrow plasma. There were significant decreases of VEGF and HGF levels and a significant increase in TSP-1 concentrations in the bone marrow plasma of patients who achieved complete or very good partial response in contrast to those who had partial or no response. VEGF and HGF levels decrease but those of TSP-1 increase after successful treatment for MM, indicating a reduction in the rate of angiogenesis.     

Circulating and progenitor endothelial cells are abnormal in patients with different types of von Willebrand disease and correlate with markers of angiogenesis

von Willebrand disease (VWD) is the most common inherited bleeding disorder and is caused by quantitative or qualitative defects of von Willebrand factor (VWF). VWF, synthesized by endothelium and megakaryocytes (MK), circulates in plasma and is present in subendothelium and platelets. Circulating endothelial cells (CEC) and progenitor endothelial cells (EPC) have been recently proposed as markers of peripheral and bone marrow-derived angiogenesis. To evaluate the association of CEC/EPC with known inherited defects of cellular and circulating VWF, we have measured the number of CEC/EPC together with cytokines involved in angiogenesis in different VWD types. A group of 74 patients was composed by the following VWD types: VWD1 (n = 22), VWD2A (n = 9), VWD2B (n = 19), VWD2M (n = 17), and VWD3 (n = 7). Healthy individuals (n = 20) were used as controls. CEC (CD146(+) , CD31(+) , and CD45(-) ) and EPC (CD34(+) , CD133(+) , and CD45(-) ) were evaluated by flow cytometry. Circulating serum levels of VEGF, E-selectin, P-selectin, EPO, and TPO were determined by ELISA. CEC, VEGF, E-selectin, and EPO were higher and EPC lower in VWD patients than in controls (P < 0.01). Among the five groups of VWD patients and controls, a significant difference was found for CEC (one-way ANOVA: P = 0.005), EPC (P = 0.001), E-Selectin (P < 0.0001), EPO (P = 0.021), and TPO (P = 0.004): the latter was high in VWD3 patients. In VWD1, we found an inverse relationship between CEC and VWF:Ag levels (P = 0.048; R(2) = 0.19). Based on these data, CEC are increased in VWD and are associated with the high levels of cytokines involved in angiogenesis (up-regulation). EPC are decreased, suggesting down-regulation of bone marrow-derived angiogenesis in VWD.     

Evidence that C-reactive protein or IL-6 are not surrogates for all inflammatory cardiovascular risk factors in hemodialysis patients

BACKGROUND/AIMS: In otherwise healthy adults, high C-reactive protein (CRP) levels are associated with cardiovascular disease and have been linked to an inflammatory state. The presence of vascular disease is also associated with increased expression of adhesion molecules, including soluble intercellular adhesion molecule (sICAM), vascular endothelial growth factor (VEGF) and leukocyte-derived myeloperoxidase (MPO). These associations suggest potential mechanisms whereby inflammation may injure the vascular endothelium, but the recognition of how these mediators act in concert remain poorly characterized. That the prevalence of atherosclerosis and markers of inflammation are increased in renal failure patients suggests that inflammation causes accelerated vascular disease. METHODS: In hemodialysis patients, we examined the relationships between plasma CRP and sICAM, VEGF and MPO longitudinally. We determined whether episodes of a high CRP value were paralleled by simultaneous increases in mediators of inflammatory injury or molecules associated with endothelial cell adhesion or growth and whether CRP levels correlated with those of VEGF and MPO. RESULTS: Episodic increases in CRP were accompanied by higher levels of VEGF, sICAM and MPO. However, there was no correlation between serum CRP levels or other acute phase proteins and either MPO or VEGF, nor was there a constant temporal relationship between MPO and CRP. By contrast, MPO and VEGF levels were closely correlated with one another during episodes of inflammation (p = 0.0001), and CRP and interleukin-6 levels were also correlated. Increases in MPO tended to be restricted to patients with grafts or catheters, and not those with AV fistulas. CONCLUSIONS: These results suggest that high plasma levels of CRP or other acute phase proteins in cross-sectional studies should be interpreted cautiously when defining mechanisms underlying cardiovascular disease in the hemodialysis patient population. One, or more than one inflammatory repertoire may be activated, one involving hepatic acute phase proteins and the other neutrophil activation and each may contribute separately to outcomes. Better prognostic information may be obtained by measurement of more markers than CRP alone, such as MPO and VEGF.     

Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation

OBJECTIVES: We sought to test the hypothesis that there is a relationship between inflammation and the prothrombotic state in atrial fibrillation (AF). BACKGROUND: Atrial fibrillation is associated with a prothrombotic or hypercoagulable state, which may contribute to an increased risk of stroke and thromboembolism. Inflammation may be involved in the pathogenesis of AF, but the role of inflammation in the pathophysiology of the prothrombotic state of AF has not been studied in detail, despite evidence of a link between inflammation and arterial atherothrombotic disorders. METHODS: We measured plasma indexes of inflammation (C-reactive protein [CRP] and interleukin-6 [IL-6]) and the prothrombotic state, including markers of platelet activation (soluble P-selectin), endothelial damage/dysfunction (von Willebrand factor), the coagulation cascade (tissue factor [TF], fibrinogen), and indexes of blood rheology (plasma viscosity, plasma fibrinogen, and hematocrit) in 106 patients with chronic AF and 41 healthy control subjects included in a cross-sectional analysis. RESULTS: Compared with controls, AF patients had higher levels of IL-6 (p = 0.034), CRP (p = 0.003), TF (p = 0.019), and plasma viscosity (p = 0.045). Plasma IL-6 levels were higher among AF patients at "high" risk of stroke (p = 0.003). After adjusting for potential confounding clinical variables (e.g., vascular disease), AF remained significantly associated with a raised logarithmic transformation (log) of TF (p = 0.04), but the relationships between AF and log IL-6, log CRP, and plasma viscosity became nonsignificant. Among AF patients, log TF (p < 0.001) and high stroke risk (p = 0.003) were independent associates of log IL-6 (adjusted r(2) = 0.443), whereas log fibrinogen (p < 0.001) and plasma viscosity (p = 0.04) were independent associates of log CRP (adjusted r(2) = 0.259). CONCLUSIONS: Increased plasma IL-6, CRP, and plasma viscosity support the case for the existence of an inflammatory state among "typical" populations with chronic AF. These indexes of inflammation are related to indexes of the prothrombotic state and may be related to the clinical variables of the patients (underlying vascular disease and co-morbidities), rather than simply to the presence of AF itself.     

Inflammation and angiogenesis in osteoarthritis

OBJECTIVE: To quantify the relationship between inflammation and angiogenesis in synovial tissue from patients with osteoarthritis (OA). METHODS: Hematoxylin and eosin staining and histologic grading for inflammation were performed for 104 patients who met the American College of Rheumatology criteria for OA and had undergone total joint replacement or arthroscopy. A purposive sample of synovial specimens obtained from 70 patients was used for further analysis. Vascular endothelium, endothelial cell (EC) proliferating nuclei, macrophages, and vascular endothelial growth factor (VEGF) were detected by immunohistochemical analysis. Angiogenesis (EC proliferation, EC fractional area), macrophage fractional area, and VEGF immunoreactivity were measured using computer-assisted image analysis. Double immunofluorescence histochemical analysis was used to determine the cellular localization of VEGF. Radiographic scores for joint space narrowing and osteophyte formation in the knee were also assessed. RESULTS: Synovial tissue samples from 32 (31%) of 104 patients with OA showed severe inflammation; thickened intimal lining and associated lymphoid aggregates were often observed. The EC fractional area, EC proliferation, and VEGF immunoreactivity all increased with increasing histologic inflammation grade and increasing macrophage fractional area. In the synovial intimal lining, VEGF immunoreactivity was localized to macrophages and increased with increasing EC fractional area and angiogenesis. No inflammation or angiogenic indices were significantly correlated with radiographic scores. CONCLUSION: Inflammation and angiogenesis in the synovium are associated with OA. The angiogenic growth factor VEGF generated by the inflamed synovium may promote angiogenesis, thereby contributing to inflammation in OA.     

Humoral markers of inflammation and endothelial dysfunction in relation to adiposity and in vivo insulin action in Pima Indians

Several studies have shown that humoral markers of inflammation and endothelial dysfunction are predictive of macrovascular events, and correlated with indirect measures of adiposity and insulin action, thus providing a possible link between obesity, insulin resistance and atherosclerosis. We examined the relationship between humoral markers of inflammation and endothelial dysfunction and direct measures of adiposity and insulin action in Pima Indians, a population with a very high prevalence of obesity and insulin resistance, but a relatively low propensity for atherosclerotic disease. Fasting plasma concentrations of the inflammatory markers C-reactive protein (CRP), secretory phospholipase A2 (sPLA2) and soluble intercellular adhesion molecule-1 (sICAM-1) and of the endothelial markers E-selectin and von Willebrand factor (vWF) were measured in 32 non-diabetic Pima Indians (18 M/14 F, age 27+/-1 years) in whom percent body fat and insulin-stimulated glucose disposal (M) were assessed by DEXA and a hyperinsulinemic clamp, respectively. CRP, sPLA2, and sICAM-1 were all positively correlated with percent body fat (r=0.71, 0.57, and 0.51, all P<0.01). E-selectin and vWF were not correlated with percent body fat, but were negatively correlated with M (r= -0.65 and -0.46, both P<0.001) and positively correlated with CRP (r=0.46, and 0.33, both P<0.05). These findings indicate that humoral markers of inflammation increase with increasing adiposity in Pima Indians whereas humoral markers of endothelial dysfunction increase primarily in proportion to the degree of insulin resistance and inflammation. Thus, obesity and insulin resistance appear to be associated with low-grade inflammation and endothelial dysfunction, respectively, even in an obesity- and diabetes-prone population with relatively low propensity for atherosclerosis.     

Angiogenesis regulatory factors in the vitreous from patients with proliferative diabetic retinopathy

We determined the levels of the endogenous angiogenesis inhibitors soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), thrombospondin (TSP)-1 and TSP-2 in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and correlated their levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF). Vitreous samples from 30 PDR and 25 nondiabetic patients were studied by enzyme-linked immunosorbent assay. TSP-1 was not detected. VEGF and TSP-2 levels were significantly higher in PDR with active neovascularization compared with inactive PDR and nondiabetic patients (P < 0.001 for both comparisons). VEGF, sVEGFR-1 and TSP-2 levels were significantly higher in PDR with hemorrhage compared with PDR without hemorrhage and nondiabetic patients (P = 0.0063; 0.0144; <0.001, respectively). VEGF and sVEGFR-1 levels were significantly higher in PDR without traction retinal detachment (TRD) compared with PDR with TRD and nondiabetic patients (P = 0.038; 0.022, respectively). TSP-2 levels were significantly higher in PDR with TRD compared with PDR without TRD and nondiabetic patients (P < 0.001). There was a significant correlation between levels of VEGF and sVEGFR-1 (r = 0.427, P = 0.038). Our findings suggest that upregulation of sVEGFR-1 and TSP-2 may be a protective mechanism against progression of angiogenesis associated with PDR. TSP-2 might be associated with TRD.     

Endothelial von Willebrand factor regulates angiogenesis

The regulation of blood vessel formation is of fundamental importance to many physiological processes, and angiogenesis is a major area for novel therapeutic approaches to diseases from ischemia to cancer. A poorly understood clinical manifestation of pathological angiogenesis is angiodysplasia, vascular malformations that cause severe gastrointestinal bleeding. Angiodysplasia can be associated with von Willebrand disease (VWD), the most common bleeding disorder in man. VWD is caused by a defect or deficiency in von Willebrand factor (VWF), a glycoprotein essential for normal hemostasis that is involved in inflammation. We hypothesized that VWF regulates angiogenesis. Inhibition of VWF expression by short interfering RNA (siRNA) in endothelial cells (ECs) caused increased in vitro angiogenesis and increased vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2)-dependent proliferation and migration, coupled to decreased integrin αvβ3 levels and increased angiopoietin (Ang)-2 release. ECs expanded from blood-derived endothelial progenitor cells of VWD patients confirmed these results. Finally, 2 different approaches, in situ and in vivo, showed increased vascularization in VWF-deficient mice. We therefore identify a new function of VWF in ECs, which confirms VWF as a protein with multiple vascular roles and defines a novel link between hemostasis and angiogenesis. These results may have important consequences for the management of VWD, with potential therapeutic implications for vascular diseases.     

Secondhand smoke (SHS) exposure is associated with circulating markers of inflammation and endothelial function in adult men and women

AimsSecondhand smoke (SHS) exposure is associated with elevated CHD risks. Yet the pathways through which this may operate have not been investigated in epidemiologic studies with objective SHS exposure measures and a wide range of CHD risk factors associated with active smoking. Therefore we investigate associations between SHS exposure and CHD risk factors, to clarify how SHS exposure may raise risk of CHD.MethodsCross-sectional population-based study of 5029 men and women aged 59–80 years from primary care practices in Great Britain. Smoking, behavioural and demographic information was reported in questionnaires; nurses made physical measurements and took blood samples for analysis of serum cotinine and markers of inflammation, hemostasis and endothelial dysfunction.ResultsActive cigarette smokers had lower albumin and higher triglycerides, CRP, IL-6, white cell count, fibrinogen, blood viscosity, factor VIII, VWF and t-PA than non-smokers. Among non-smokers, serum cotinine levels were independently positively associated with CRP, fibrinogen, factor VIII, VWF and t-PA and inversely associated with albumin, after adjustment for age, gender, social and behavioural factors. The differences in CRP, fibrinogen and albumin between cotinine ≤0.05 and >0.7 ng/ml were one-third to one half the size of differences between cotinine ≤0.05 ng/ml and current smokers, but were of similar magnitude for VWF and t-PA.ConclusionsEndothelial, inflammatory and haemostatic markers related to CHD risk showed independent associations with SHS exposure in the same direction as those for active smoking. Results aid understanding of the associations between SHS exposure and elevated CHD risks.     

肾上腺皮质肿瘤VEGF、TSP-1的表达及其与微血管密度的关系

目的 研究血管内皮生长因子(VEGF)、血小板反应素1(TSP-1)在肾上腺皮质肿瘤中的表达及其与微血管密度(MVD)的关系.方法 采用免疫组化方法检测13例肾上腺皮质癌、30例肾上腺皮质腺瘤和7例正常肾上腺组织中VEGF、TSP-1及MVD(以CD34为标记)的表达.结果 肾上腺皮质癌VEGF表达高于肾上腺皮质腺瘤,差异有统计学意义(P＜0.01);TSP-1在正常肾上腺皮质表达明显高于肾上腺皮质癌(P＜0.01);MVD在肾上腺皮质癌为(107.67±11.91)/视野,显著高于肾上腺皮质腺瘤(59.46±21.31)/视野和正常肾上腺皮质组织(25.10±3.94)/视野(均P＜0.01);VEGF的表达与MVD呈正相关(P＜0.01),TSP-1的表达与MVD呈负相关(P＜0.01),VEGF与TSP-1的表达呈负相关(P＜0.01).结论 VEGF和TSP-1在肾上腺皮质肿瘤的表达失衡是其肿瘤血管异常生成的重要原因.     

乳腺癌患者血清VEGF含量测定及临床意义

血管内皮生长因子 (VEGF)在肿瘤血管的形成中起到非常重要的作用。本研究采用 EL ISA法检测 36例乳腺癌患者术前血清血管内皮生长因子 (VEGF)含量 ,与良性对照组及正常对照组比较 ,并观察 VEGF与临床病理指标的关系。认为乳腺癌组与良性对照组和正常对照组比较有非常显著差异 ,并与临床分期及淋巴结转移有相关性。     

Relationship between inflammatory markers and clinical patterns of atrial fibrillation in patients with congestive heart failure

BACKGROUND: Occurence of atrial fibrillation (AF) adversely affects left atrial size and cardiac function. This arrhythmia is also associated with an increase of plasma CRP and fibrinogen concentration. It is not clear whether elevated levels of inflammatory markers in patients with congestive heart failure (CHF) are associated with AF, clinical symptoms or adverse cardiac remodelling. AIM: To investigate the association between levels of inflammatory markers and selected clinical and echocardiographic parameters as well as used treatment in the population of CHF patients with various forms of AF. METHODS: The cross-sectional study included 99 patients with CHF divided into 3 groups. Group I included patients with sinus rhythm. Group II consisted of patients admitted to hospital with AF and discharged with sinus rhythm (the category of paroxysmal and persistent AF). Group III comprised patients with permanent AF. In all patients plasma CRP and fibrinogen concentrations were measured and echocardiographic examination was carried out. Left atrial dimension (LA), ejection fraction (LVEF) and right ventricular systolic pressure (RVSP) were assessed. RESULTS: Mean CRP concentration in group III (5.83+/-5.36 mg/l) was significantly higher than in group I (p=0.001) and group II (p=0.033). In the group with permanent AF mean fibrinogen concentration was elevated to a higher level (391.0+/-77.3 mg/dl) than in group II (p=0.007) and group I (p=0.099). Mean LA and RV dimensions and RVSP in group III were significantly higher than in group I and group II. Multivariable analysis revealed that plasma CRP concentration was significantly associated with the presence of arterial hypertension (p <0.001) and LA enlargement (p=0.007). A significant association between fibrinogen level and CRP level (p=0.038), presence of permanent AF (p=0.045) and metabolic syndrome (p <0.05) was found. Values of ln CRP were significantly correlated with LA diameter (r=0.24; p=0.015). CONCLUSIONS: Increased plasma CRP level in patients with CHF were significantly associated with arterial hypertension and LA enlargement. Permanent form of AF and CRP level have been shown to be significantly associated with increased plasma fibrinogen concentration in the course of CHF.     

The role of inflammation, humoral and cell mediated autoimmunity in the pathogenesis of atherosclerosis

The pathogenesis of atherosclerosis has not been well defined and many questions remain unanswered. Many studies have discussed the importance of inflammation as the first step in promoting endothelial dysfunction and atherosclerosis.The association of inflammatory markers such as fibrinogen and C reactive protein (CRP) with atherosclerosis and cardiovascular/cerebrovascular clinical events reinforces the pivotal role that inflammation plays in the atherosclerotic process.The humoral and cellular autoimmune response against antigens expressed in the endothelium and the greater prevalence of atherosclerosis in immune-mediated rheumatic diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) strongly suggest the involvement of autoimmunity in the atherosclerotic process. The role of inflammation and autoimmune responses in atherosclerosis are discussed in order to better understand their close link on its pathogenesis.     

慢性充血性心力衰竭患者血清可溶性细胞间粘附分子-1的变化及与C-反应蛋白的相关性分析

目的了解慢性充血性心力衰竭(心衰)患者血清可溶性细胞间粘附分子-1(sICAM-1)的变化及与C-反应蛋白(CRP)的相关性.方法测定60例心衰患者和20例健康人的血清sICAM-1及CRP水平.比较分析心衰患者及不同程度心衰患者之间sICAM-1、CRP水平的变化,以及sICAM-1与CRP的相关性.结果心衰患者血清sICAM-1及CRP水平明显高于健康对照组(P＜0.01),二者均随心衰程度加重而增高,呈高度正相关(r=0.68,P＜0.01).不同程度心衰患者之间血清sICAM-1及CRP水平差异有显著性(P＜0.05).结论心衰患者存在着免疫激活和心肌炎症反应,心衰程度愈重,炎症反应愈明显.     

The relationship between plasma asymmetrical dimethyl-L-arginine and inflammation and adhesion molecule levels in subjects with normal, impaired, and diabetic glucose tolerance

Increasing evidence suggests that the postprandial state is a contributing factor to the development of atherosclerosis. To evaluate the effects of acute hyperglycemia on endothelial dysfunction and inflammation, plasma asymmetrical dimethyl-l-arginine (ADMA), intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, and C-reactive protein (CRP) levels and secretory phospholipase A(2) (sPLA(2)) activities were measured in subjects with normal (n = 35), impaired (IGT) (n = 25), and diabetic (DGT) (n = 20) glucose tolerance. At baseline, plasma ADMA, sICAM-1, and CRP concentrations and plasma sPLA(2) activities were higher in both the IGT and DGT groups than in the normal glucose tolerance group (for each comparison, each P < .001). Patients with DGT have higher plasma ADMA and sICAM-1 concentrations than patients with IGT (for each, P < .001).Two hours after glucose loading, plasma ADMA and CRP concentrations and sPLA(2) activities were significantly elevated in the 3 groups when compared with baseline levels (for each comparison, P < .001). Plasma vascular cell adhesion molecule 1 and sICAM-1 concentrations were found to be elevated from baseline levels after glucose loading in the IGT and DGT groups (for each comparison, P < .001). Correlation analysis at baseline suggested that there was a significant relationship between ADMA and inflammation and soluble adhesion markers in the studied groups. In conclusion, plasma concentrations of ADMA and of inflammation and adhesion molecules were elevated in the prediabetic state. A complex interrelation could exist between ADMA and inflammation, and mechanisms involved in endothelial dysfunction are multifactorial at the prediabetic and diabetic state.     

VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients

Platelets sequester angiogenesis regulatory proteins which suggests an avenue for developing biomarkers to monitor disease. We describe a comparison of angiogenesis regulatory proteins found in platelets of colorectal cancer patients and normal controls. Platelet and plasma content of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin-1 (TSP-1) and endostatin in 35 patients with colon cancer were compared with 84 age-matched healthy controls using ELISAs. We standardized the platelet preparation procedure, introduced process controls and normalized the respective protein levels to platelet numbers using an actin ELISA. Statistically significant differences were found in the median levels of VEGF, PF4 and PDGF in platelets of patients with cancer compared to healthy individuals. Platelet concentrations in cancer patients versus controls were: VEGF 1.3 versus 0.6 pg/10⁶, PF4 18.5 versus 9.4 ng/10⁶, and PDGF 34.1 versus 21.0 pg/10⁶. Multivariable logistic regression analysis indicated that PDGF, PF4 and VEGF were independent predictors of colorectal carcinoma and as a set provided statistically significant discrimination (area under the curve = 0.893, P < .0001). No significant differences were detected for bFGF, endostatin, or TSP-1. Reference Change Value analysis determined that the differences seen were not clinically significant. Plasma levels yielded no correlations.