scholarly journals Rosiglitazone Influences the Expression of Leukocyte Adhesion Molecules and CD14 Receptor in Type 2 Diabetes Mellitus Patients

2014 ◽  
pp. S293-S298 ◽  
Author(s):  
T. ŠTULC ◽  
H. SVOBODOVÁ ◽  
Z. KRUPIČKOVÁ ◽  
R. DOLEŽALOVÁ ◽  
I. MARINOV ◽  
...  

Diabetes mellitus is associated with increased inflammatory response, which may contribute to atherosclerosis progression. Experimental results demonstrated anti-inflammatory activity of glitazones; their effect on leukocyte adhesion molecules has not been studied to date. We therefore studied the effect of rosiglitazone treatment on leukocyte surface expression of adhesion molecules in patients with type 2 diabetes mellitus and compared our results with findings in healthy subjects. 33 subjects with type 2 diabetes and 32 healthy controls were included; patients were examined at baseline and after 5 months of rosiglitazone treatment (4 mg/d). Leukocyte expression of adhesion molecules LFA-1, CD18 and ICAM-1 was quantified using flow cytometry; in addition, CD14 (lipopolysaccharide receptor) expression was analyzed as a marker of nonspecific immunity. The expression of examined molecules at baseline was higher in patients compared to controls. Despite only mild decrease in blood glucose, rosiglitazone treatment induced substantial decrease of CD18 and CD14 expression and borderline decrease of LFA-1 and ICAM-1 expression (on monocytes only). We thus observed improvement in the expression of leukocyte inflammatory markers after rosiglitazone treatment. This effect is supposed to be mediated by direct effect of rosiglitazone on PPAR-γ receptors on leukocytes.

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051989385
Author(s):  
Gehan A Hegazy ◽  
Zuhier Awan ◽  
Enayat Hashem ◽  
Nabil Al-Ama ◽  
Asmaa Basha Abunaji

Objective Type 2 diabetes mellitus (T2DM) is a main risk factor for development of cardiovascular diseases (CVDs) and endothelial dysfunction. This study aimed to investigate serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), and endothelium selectin (sE-selectin) in T2DM patients with macrovascular complications. Methods A cross-sectional study of 21 controls, 30 T2DM patients without CVDs, and 30 T2DM patients with CVDs was conducted. Serum levels of soluble adhesion molecules including sVCAM-1, sICAM-1, and sE-selectin were determined using ELISA. Results Serum levels of sVCAM-1, sICAM-1, and sE-selectin were higher in T2DM patients than in controls. Levels of serum sVCAM-1 were higher in T2DM patients with CVDs compared with T2DM patients without CVDs. In T2DM patients with CVDs, significant positive associations were observed between sVCAM-1, sICAM-1, and sE-selectin levels (r = 0.575, p = 0.001 and r = 0.378, p = 0.040). Conclusions Circulating levels of soluble adhesion molecules were elevated in T2DM patients, regardless of whether the patients had cardiovascular complications. Only sVCAM-1 was considered a useful marker for the prediction of CVDs in T2DM patients.


Author(s):  
Eleonora Palella ◽  
Rossella Cimino ◽  
Salvatore A. Pullano ◽  
Antonino S. Fiorillo ◽  
Elio Gulletta ◽  
...  

Background: Type 2 diabetes mellitus (T2DM) is characterized by a prothrombotic state, predisposing to vascular complications. Some related markers, linking thrombophilia to hemostasis and inflammation, however, have been poorly explored in relation to patients’ glycemia. We therefore investigated the association of laboratory hemostatic parameters, circulating adhesion molecules (ADMs), white blood cell (WBC) count, and neutrophil/lymphocyte ratio (NLR) with T2DM and glycemic control. Research design: In this study, 82 subjects, grouped into T2DM patients (n = 41) and healthy individuals (n = 41) were enrolled. To evaluate glycemic control, the T2DM cohort was expanded to 133 patients and sub-classified according to glycated hemoglobin (HbA1c) <7% and ≥ 7% (n = 58 and n = 75, respectively). We assessed glycemia, HbA1c, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), platelet and leukocyte parameters, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and selectins (E-, P-, L-). Results: PT % activity, PAI-1, VCAM-1, WBC, and neutrophil counts were significantly higher in T2DM patients than in healthy subjects. Poor glycemic control (HbA1c ≥ 7%) was correlated with increased PT activity (p = 0.015), and higher levels of E-selectin (p = 0.009), P-selectin (p = 0.012), and NLR (p = 0.019). Conclusions: Both T2DM and poor glycemic control affect some parameters of hemostasis, inflammation, and adhesion molecules. Further studies are needed to establish their clinical utility as adjuvant markers for cardio-vascular risk in T2DM patients.


2017 ◽  
Vol 70 (11-12) ◽  
pp. 437-443
Author(s):  
Romana Mijovic ◽  
Branislava Ilincic ◽  
Suncica Kojic-Damjanov ◽  
Biljana Vuckovic ◽  
Radmila Zeravica ◽  
...  

Introduction. Endothelium is a dynamic, strategically positioned defensive regulator of vascular homeostasis. Physiology and Pathophysiology of Vascular Endothelium. Endothelial phenotypic modulation involves five basic characteristics: the expression of leukocyte adhesion molecules, the production of cytokines, change in the shape and the permeability of the endothelium, prothrombotic changes and upregulation of autoantigens. Obesity, Metabolic Inflammation and Vascular Endothelium One of the most important pathophysiological manifestations of adiposopathy may be the phenotypic conversion of vascular endothelium. Insulin Resistance and Vascular Endothelium. Under the conditions of insulin resistance and consequent hyperinsulinemia, there is imbalance between the production of endothelial vasoconstrictors and vasodilators, increased expression of adhesion molecules, and platelet hyperreactivity. Hyperglycemia and Vascular Endothelium. Hyperglycemia causes endothelial dysfunction by various mechanisms that involve activation of polyol pathway and production of sorbitol, increased formation of advanced glycation end products, activation of various isoforms of protein kinase C and activation of hexosamine pathway. Dyslipidemia and vascular endothelium. Dyslipidemia takes an important role in a cascade of pathophysiological processes that result in endothelial activation and chronic dysfunction. Conclusion. Hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia, visceral obesity and low-grade inflammation are the main factors responsible for development of endothelial dysfunction in type 2 diabetes mellitus.


Circulation ◽  
2002 ◽  
Vol 106 (6) ◽  
pp. 679-684 ◽  
Author(s):  
Steven M. Haffner ◽  
Andrew S. Greenberg ◽  
Wayde M. Weston ◽  
Hongzi Chen ◽  
Ken Williams ◽  
...  

2009 ◽  
pp. 701-707
Author(s):  
H Svobodová ◽  
T Štulc ◽  
Z Kasalová ◽  
R Doležalová ◽  
I Marinov ◽  
...  

Diabetes mellitus is associated with a number of prothrombotic abnormalities, and correction of these abnormalities might translate into the reduction of cardiovascular risk. Glitazones improve endothelial function and reduce inflammation, but much less is known about their effect on thrombogenic factors. We have therefore studied the effect of rosiglitazone on leukocyte and soluble thrombogenic markers in patients with type 2 diabetes mellitus. Thirty-three subjects with type 2 diabetes and 32 normal controls were included; patients were examined at baseline and after 5 months of rosiglitazone treatment (4 mg/day). We measured leukocyte-platelet aggregates and leukocyte expression of either P-selectin glycoprotein ligand 1 (PSGL-1) or receptor for urokinase-type plasminogen activator (uPAR) using flow cytometry, as well as several circulating soluble thrombogenic markers by ELISA method. Leukocyte expression of uPAR and PSGL-1 was significantly higher in patients than in controls. Leukocyte-platelet aggregates and leukocyte expression of uPAR and PSGL-1 significantly decreased after rosiglitazone. There was also significant decrease in CRP and fibrinogen levels, but there was no effect of diabetes and/or rosiglitazone on other circulating molecules. In conclusions, we observed a substantial improvement in the expression of thrombogenic markers on leukocytes after rosiglitazone treatment, suggesting the novel antithrombotic effects of rosiglitazone.


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