Plasma Concentrations Of Adhesion Molecules Research Articles

Baseline and overtime variations of soluble adhesion molecule plasma concentrations are associated with mobility recovery after rehabilitation in multiple sclerosis patients

Rehabilitative exercise outcomes and plasma concentrations of soluble adhesion molecules (sEndoglin, sE-Selectin, sL-Selectin, sICAM-1, sNCAM, sNCAM-1, sVCAM-1, sPECAM-1, sVAP-1) were evaluated in 60 severely disabled progressive multiple sclerosis (MS) patients at 4-time points. Changes of sE-Selectin, sL-Selectin, and sPECAM-1 concentrations were observed over time, and their variations were significantly correlated with rehabilitative outcome variations. Baseline sVAP-1 concentrations were able to predict functional mobility recovery. Our data suggest that the evaluation of adhesion molecules in plasma provides useful information to interpret rehabilitative exercise processes and to identify potential predictors of the rehabilitation-induced changes in mobility outcomes in MS patients.

Cardiotrophin-1 induces intercellular adhesion molecule-1 expression by nuclear factor κB activation in human umbilical vein endothelial cells

In addition to elevated concentrations of cytokines, patients with congestive heart failure (CHF) show endothelial dysfunction and increased plasma concentrations of adhesion molecules like intercellular adhesion molecule-1 (ICAM-1). Furthermore, the concentration of cardiotrophin-1 (CT-1)--a cytokine of the interleukin-6 superfamily--is increased in CHF. We tested the hypothesis whether CT-1 is able to induce ICAM-1 in human umbilical vein endothelial cells (HUVEC). Furthermore we examined the signalling mechanisms of CT-1 mediated ICAM-1 expression. Confluent layers of HUVEC were incubated with increasing concentrations of CT-1 (5 to 100 ng/ml) for different periods. ICAM-1 mRNA was determined by real-time polymerase chain reaction (PCR) and ICAM-1 surface expression by fluorescence-activated cell sorter (FACS) analysis and soluble ICAM-1 (sICAM-1) in the culture supernatant by enzyme linked immunosorbent assay (ELISA). To clarify the signalling pathway of CT-1 induced ICAM-1 expression we used various inhibitors of possible signal transducing molecules, electromobility shift assay (EMSA) and Western blot analysis. CT-1 induced ICAM-1 mRNA (1.8 +/- 0.8 fold increase compared to unstimulated cells after 6 hours) and protein (1.4 +/- 0.2 fold increase compared to unstimulated cells after 48 hours) in HUVEC in a time- and concentration-dependent manner. EMSA experiments show that CT-1 causes nuclear factor (NF) kappaB activation. Because parthenolide could inhibit CT-1 induced ICAM-1 expression NFkappaB activation is required in this pathway. CT-1 did not activate extracellular signal regulated kinases (ERK), c-Jun N-terminal kinase (JNK) and p38. CT-1 is able to induce ICAM-1 in endothelial cells by NFkappaB activation. These results may explain in part elevated ICAM-1 concentrations in patients with CHF and endothelial dysfunction.

Beneficial Effects of a 4-Week Exercise Program on Plasma Concentrations of Adhesion Molecules

Plasma concentrations of adhesion molecules are elevated in patients with endothelial dysfunction and atherosclerosis (1), as well as in patients with impaired glucose tolerance (IGT) or type 2 diabetes—even those without angiographic evidence for atherosclerosis (2). Physical activity is associated with reduced risk of cardiovascular disease and total mortality in men with type 2 diabetes (3). The beneficial effects of physical activity could be mediated by improved markers of endothelial dysfunction, including adhesion molecules. We therefore tested the hypothesis that an intensive 4-week physical training program leads to improved plasma concentrations of intracellular …

Effect of Propionylcarnitine on Changes in Endothelial Function and Plasma Levels of Adhesion Molecules Induced by Acute Exercise in Patients with Intermittent Claudication

In patients with intermittent claudication, treadmill exercise may cause acute deterioration of endothelial function and increase in plasma concentrations of adhesion molecules. The authors evaluated the efficacy of intravenously administered propionylcarnitine (PLC)in preventing these phenomena. Thirty-six claudicants with postexercise decrease in brachial artery flow-mediated dilation (FMD)were randomized to either placebo or PLC (600 mg as a single bolus followed by 1 mg/kg/min for 60 minutes).In the 18 patients randomized to placebo, FMD markedly decreased with exercise before (from 6.8 +/-0.4% to 4.0 +/-0.4%; p < 0.001) and after treatment (from 6.5 +/-0.4% to 4.4 +/-0.5%; p < 0.001). By contrast, in the PLC group, FMD significantly decreased with exercise before treatment (from 8.0 +/-0.7% to 4.4 +/-0.4%; p < 0.001), but not after active drug administration (from 7.1 +/-0.7% to 6.0 +/-0.6%; p = 0.067). The difference between treatments was not significant (p = 0.099; ANOVA). However, in the PLC group, the authors found that the greater the exercise-induced deterioration in endothelial function before treatment, the greater the capacity of PLC to prevent a postexercise decrease in FMD (r = -0.50, p = 0.034). Accordingly, they analyzed data in the 19 patients with a baseline exercise-induced decrease in FMD >or=45% (ie, the median FMD reduction in the entire group of 36 patients), and found that the exercise-induced FMD decrease was less after PLC than after placebo (p = 0.046, ANOVA). In the same subgroup, the exercise-induced increase in plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) was significantly higher before than after treatment in patients randomized to PLC (23.4 +/-5% vs 15.3 +/-7%, p = 0.007). In conclusion, in patients with intermittent claudication suffering from a greater endothelial derangement after treadmill, PLC administration provided a protective effect against deterioration of FMD and increase of sVCAM-1 induced by exercise.

No increase in C-reactive protein levels during intranasal compared to oral hormone therapy in healthy post-menopausal women

Inflammation plays an important role in the development of atherosclerotic disease. Oral post-menopausal hormone therapy increases serum C-reactive protein (CRP) levels. This study compared the effects of intranasal and oral administration of 17beta-estradiol (E2) combined with norethisterone acetate (NETA) on markers of inflammation in healthy post-menopausal women. Ninety healthy post-menopausal women (age 56.6 +/- 4.7 years) participated in this 1-year trial. After computerized block randomization, they daily received, in a double-blind fashion, either intranasal E2/NET [175 microg/275 microg (n = 47)] or oral E2/NETA [1 mg/0.5 mg (n = 43)]. Concentrations of high sensitivity CRP and adhesion molecules were measured at baseline and after 12, 24 and 52 weeks of treatment. CRP levels were increased (P = 0.001) in the oral but not in the intranasal group. The increase in the oral group was highest at week 12 (64.9%) and was larger (P < 0.01) compared with the non-significant increase (8.6%) found in the intranasal group. Both groups showed decreases (P < 0.001) in soluble vascular cell adhesion molecule (sVCAM), soluble intracellular adhesion molecule (sICAM) and sE-selectin. The decreases were larger (P < 0.01) in the oral than in the intranasal group. Intranasal E2/NET therapy did not significantly increase CRP levels, in contrast to the increase observed in the oral E2/NETA treatment group. Both intranasal and oral therapy lowered plasma concentrations of adhesion molecules, however, more so in the oral group.

Near Normalization of Adhesion Molecule Plasma Concentrations after a 4-Weeks Physical Training Program in Patients with Abnormal Glucose Tolerance

Near Normalization of Adhesion Molecule Plasma Concentrations after a 4-Weeks Physical Training Program in Patients with Abnormal Glucose Tolerance

Dexamethasone-eluting stents and plasma concentrations of adhesion molecules in patients with unstable coronary syndromes: Results of the historically controlled SESAME study

Plasma concentrations of intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin may increase after percutaneous coronary intervention (PCI). The aim of this study was to assess whether anti-inflammatory treatment with steroid-eluting stents influenced concentrations of adhesion molecules after PCI in patients with unstable coronary syndromes. Consecutive patients with unstable coronary syndromes who were prospectively assigned to undergo implantation of a dexamethasone-eluting stent were compared with a control group of consecutive historical patients who received a similar non-drugeluting stent in the period immediately preceding availability of the steroid-eluting stents. Circulating concentrations of adhesion molecules were measured before the procedure and at 6 and 24 hours after implantation. The study included 50 patients who received the dexamethasone-eluting stent (41 men, 9 women; mean [SD] age, 60 [9] years) and 50 historical controls who received the non-drug-eluting stent (40 men, 10 women; mean age, 63 [11] years). Baseline values for the adhesion molecules were similar in the 2 groups: in patients who received the dexamethasone-eluting stent, mean (SD) values were 210 (41) ng/mL for ICAM-1, 637 (119) ng/mL for VCAM-1, and 46 (9) ng/mL for E-selectin; in the control group, the corresponding values were 218 (42), 618 (140), and 43 (10) ng/mL. Circulating concentrations at 24 hours were significantly lower in patients receiving the drug-eluting stent compared with controls for both ICAM-1 (279 [49] vs 338 [60] ng/mL, respectively; P = 0.001) and VCAM-1 (772 [163] vs 896 [207] ng/mL; P = 0.004). There was no significant between-group difference in E-selectin concentrations at 24 hours (60 [10] vs 56 [11] ng/mL). In this study, dexamethasone-eluting stents reduced plasma concentrations of ICAM-1 and VCAM-1 after PCI in patients with unstable coronary syndromes compared with historical controls.

Influence of irbesartan on plasma concentrations of adhesion molecules and chemokines in coronary heart disease with documented coronary atherosclerosis

To analyze the antithrombin-III (AT-III) activity in the plasma in relation to the serum albumin and total protein in preeclampsia and gestational hypertension.The medical records of 139 patients who were diagnosed with gestational hypertension (n = 33) and preeclampsia (n = 106) were reviewed, and the relationships between the activity of AT-III and serum albumin or total protein were evaluated.The plasma AT-III activity in gestational hypertension and preeclampsia was correlated with the serum albumin and TP levels.There were significant correlations between AT-III activity and albumin in gestational hypertension (r = 0.504, p = 0.003) and preeclampsia (r = 0.343, p = 0.003). There were also significant correlations between AT-III activity and TP in gestational hypertension (r = 0.619, p = 0.001) and preeclampsia (r = 0.366, p = 0.001). Regression coefficients between AT-III and albumin and between AT-III and TP in gestational hypertension (23.7 and 14.0, respectively) were significantly steeper than those in preeclampsia (14.6 and 9.6, respectively).The plasma AT-III activity in gestational hypertension and preeclampsia was correlated with the serum albumin and TP levels. This suggests that AT-III activity is more likely to decrease in gestational hypertension than in preeclampsia.

E-selectin plasma concentration is influenced by glycaemic control in NIDDM patients: possible role of oxidative stress.

Although elevated levels of soluble E-selectin and intercellular cell adhesion molecules-1 (ICAM-1) have been reported in non-insulin-dependent diabetes mellitus (NIDDM), it is not clear by what mechanism this elevation occurs and whether or not it is related to glycaemic control. In this study we analyse: 1) the relation of glycaemic control with the concentrations of E-selectin, vascular cell adhesion molecules-1 (VCAM-1) and ICAM-1 in NIDDM patients: 2) whether metabolic control can affect the oxidative stress (as measured by plasma hydroperoxide concentration and susceptibility of LDL to in vitro oxidation) and hence the adhesion molecule plasma concentrations. Thirty-four (19 males and 15 females) poorly controlled NIDDM patients were studied. All parameters were evaluated at the beginning of the study and after 90 days of dietary and pharmacological treatment. The treatment decreased HbA1c (p < 0.001), E-selectin (p < 0.001), plasma hydroperoxides (p < 0.003) and the susceptibility of LDL to in vitro oxidation (lag phase) (p < 0.0001). Before treatment HbA1c, lag phase and lipid hydroperoxides correlated with E-selectin plasma concentration (r = 0.51, -0.57 and 0.54, respectively, p < 0.01). There was also a correlation between HbA1c and lag phase (p < 0.01) and between HbA1c and lipid hydroperoxides (p < 0.01). In addition, the variations of HbA1c, lag phase and lipid hydroperoxide values correlated with those for E-selectin concentration after 90 days' treatment (r = 0.54, -0.64 and 0.61, respectively, p < 0.01). In multiple linear correlation analysis, however, the partial correlation coefficients of HbA1c (basal and variations) with E-selectin concentration (basal and variations) fell to non-significant values (r = 0.12 and 0.25, respectively) when LDL lag phase and plasma hydroperoxides were kept constant. The results indicate that the improvement of metabolic control in NIDDM patients is associated with a decrease of E-selectin plasma levels; they also suggest that glycaemic control per se is not directly implicated in determining E-selectin plasma concentration; glycaemic control could affect E-selectin concentration through its effect on oxidative stress.

Does age influence circulating adhesion molecules in the critically ill?

Soluble adhesion molecules are regarded to be markers of inflammation, endothelial activation, or damage. The influence of age on plasma concentrations of circulating adhesion molecules should be serially studied in critically ill intensive care patients. Prospective and descriptive study over 5 days. Clinical investigation in a surgical intensive care unit of a university hospital. Thirty critically ill patients (Acute Physiology and Chronic Health Evaluation [APACHE] II score of > 15 points), with sepsis secondary to postoperative complications, were included in this study. Fifteen consecutive patients aged < 50 yrs and 15 consecutive patients aged > 70 yrs were prospectively studied. All patients were treated by the standard protocols of our intensive care unit, which did not differ between the groups. The patients received continuous analgesia-sedation and mechanical ventilation. Intensivists caring for the patients were not involved in the study and were blinded to data analysis. Hemodynamic parameters were extensively monitored in all patients. From arterial blood samples, plasma concentrations of soluble adhesion molecules (endothelial leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, granule membrane protein-140) were measured on the day of admission (i.e., baseline values) and during the following 5 days. Three of the younger patients and six of the elderly patients died during the study period (p < .05). Oxygen delivery and consumption, and the other hemodynamic data, were without group differences throughout the study. Plasma concentrations of all adhesion molecules were beyond normal at baseline in both groups. These concentrations increased further during the first 2 to 3 days in both groups, with a significantly higher increase in the elderly patients (endothelial leukocyte adhesion molecule-1 to 179 +/- 32 ng/mL; intercellular adhesion molecule-1 to 1695 +/- 158 ng/mL; vascular cell adhesion molecule-1 to 1395 +/- 212 ng/mL; and granule membrane protein-140 to 888 +/- 119 ng/mL). In the younger patients, concentrations of soluble adhesion molecules decreased later in the study and almost reached baseline values on day 5. In the elderly patients, these concentrations remained significantly higher until the end of the study. The higher plasma concentrations of the measured adhesion molecules in elderly critically ill patients indicate that elderly patients are more prone than younger patients to a more pronounced activation or even damage of the endothelium. Further work needs to be done to determine the prognostic importance and to define the role of soluble adhesion molecules, particularly in the elderly critically ill patient.