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The influence of exendin and GLP-1 on VCAM-1 and ICAM-1 production in endothelium stimulated by TNF-α and glycated albumin  [PDF]
Krzysztof Siemianowicz, Tomasz Francuz, Wojciech Garczorz
Health (Health) , 2012, DOI: 10.4236/health.2012.412A225

A growing body of evidence indicates that incretins may have pleiotropic beneficial effects beyond lowering glucose blood concentration. The effect of GLP-1 and exendin-4 on coronary arteries endothelium in diabetic and obese individuals has been studied widely. TNF-a is one of adipocytokines. The aim of our study was to evaluate the influence of glycated albumin (GlyAlb; 100; 500 and 1000 mg/L) and proinflammatory cytokine, TNF-α (2.5 and 10 ng/mL), on expression of ICAM-1 and VCAM-1 in cultured human endothelial cells derived from coronary arteries. The next goal of the study was to evaluate the influence of GLP-1 (10 nM and 100 nM) and its analogue, exendin-4 (1 nM and 10 nM), on the expression of ICAM-1 and VCAM-1 in these cell line. TNF-a statistically significantly increased VCAM-1 production by endothelial cells, whereas GlyAlb statistically significantly augmented the expression of both tested adhesion mole- cules. Exendin-4 and GLP-1 statistically significantly reduced the expression of VCAM-1 in endothelial cells stimulated by GlyAlb in dose-de- pendent manner. When TNF-a was used as the stimulant only exendin-4 in the concentration of 10 nM statistically significantly reduced the expression of VCAM-1. Studied incretins in their both concentrations statistically significantly reduced the expression of ICAM-1 in endothelial cells stimulated by GlyAlb. The influence of TNF- a on the expression of ICAM-1 was statistically significantly reduced by both concentrations of exendin-4 but only by the higher concentration of GLP-1. The results of our present study indicate that incretins may present a group of agents developing pleiotropic effects beyond the reduction of blood glucose concentration. Their vaso-protective and cardioprotective action may be of importance in diabetic and obese individuals.

Spindle Cell Hemangioma and Decorin Expression  [PDF]
Daiki Rokunohe, Hitoshi Takeda, Takahide Kaneko, Takayuki Aizu, Eijiro Akasaka, Yasushi Matsuzaki, Hajime Nakano, Daisuke Sawamura
Journal of Cosmetics, Dermatological Sciences and Applications (JCDSA) , 2012, DOI: 10.4236/jcdsa.2012.21002
Abstract: Spindle cell hemangioma (SCH) is a rare benign vascular tumor and we report 2 cases of SCH who are 50-year-old man and 16-year-old girl. A growing amount of evidence indicates that multifunctional ECM molecule decorin regulate endothelial cell-matrix interactions during angiogenesis. Furthermore, a current publication shows that no detectable decorin expression was found in the stromas of tumor nests in Kaposi’s sarcoma or angiosarcoma groups while the expression was clearly observed in the connective tissue stromas within benign vascular tumors. SCH exhibits spindle cell proliferation and resembles Kaposi’s sarcoma. Therefore, this study examined decorin expression in the tissues of our SCH cases by immunohistochemical analysis. The results demonstrated that immunoreactivity of decorin was clearly detectable in the connective tissue stroma within tumor nests. SCH was first perceived as sarcoma because of spindle cell proliferation, but this proliferation was subsequently found to be reactive. The presence of decorin expression in our cases also indicates that SCH have benign properties. Moreover, this study further increases the reliability of examination of decorin expression for differentiation between benign and malignant vascular tumors.
Nitric Oxide/Peroxynitrite Redox Imbalance in Endothelial Cells Measured with Amperometric Nanosensors  [PDF]
Andrzej Burewicz, Hazem Dawoud, Lu-Lin Jiang, Tadeusz Malinski
American Journal of Analytical Chemistry (AJAC) , 2013, DOI: 10.4236/ajac.2013.410A1004

The cytoprotective messenger nitric oxide (NO) and cytotoxic peroxynitrite (ONOO-) are the main components of oxidative stress and can be generated by endothelial cells. A tandem of electrochemical nanosensors (diameter 200-300 nm) were used to measure, in situ, the balance between NO and ONOO-produced by human umbilical vein endothelial cells (HUVEC’s). The amperometric nanosensors were placed 5 ± 2 μm from the surface of the endothelial cells and the concentration of NO and ONOO- was measured at 630 mV and -300 mV (vs Ag/AgCl) respectively. Normal, functional, endothelial cells produced maximal 450 ± 25 nmol.L-1 of NO and 180 ± 15 nmol.L-1 of ONOO- in about 3 s, after stimulation with calcium ionophore. The in situ measurements of NO and ONOO- were validated using nitric oxide synthase inhibitor L-NMMA, ONOO

Exercício físico e disfun??o endotelial
Ghisi, Gabriela Lima de Melo;Durieux, Adriana;Pinho, Ricardo;Benetti, Magnus;
Arquivos Brasileiros de Cardiologia , 2010, DOI: 10.1590/S0066-782X2010001500025
Abstract: the role of the endothelium was considered mainly as a selective barrier for the diffusion of macromolecules from the lumen of blood vessels to the interstitial space. during the last 20 years, many other functions have been defined for the endothelium, such as the regulation of the vagal tonus, the promotion and inhibition of neovascular growth and the modulation of inflammation, of platelet aggregation and coagulation. this finding is considered one of the most important concepts in modern vascular biology. currently, atherosclerosis is the prototype of the disease characterized in all its phases by an endothelial dysfunction, defined as an insufficient offer of nitric oxide (no), which predisposes the endothelium to oxidative stress, inflammation, erosion and vasoconstriction. in this sense, several experimental studies have demonstrated that physical exercise is capable of restoring and improving the endothelial function. the impact of exercise on the endothelium has been broadly discussed. considering its vasodilating effect and the risk factors, the possibility of treating coronary artery disease and its outcomes without the inclusion of physical exercise became unconceivable. however, the literature is still controversial regarding the intensity of physical effort that is necessary to cause significant protective alterations in endothelial functions. moreover, the association between intense physical exercises and increased oxygen consumption, with a consequent increase in free radical formation, is also discussed.
Endothelium derived relaxation factors reduce sulfur dioxide-induced aortic relaxation  [PDF]
Omar A. M. Al-Habib, Abbas B. Q. Salihi
Open Journal of Molecular and Integrative Physiology (OJMIP) , 2013, DOI: 10.4236/ojmip.2013.34023

The endothelium plays a key role in the control of vascular patency and tone. Thus, the main objective of the study was to determine the role of endothelium and its derived relaxation factors in mediating relaxation of rat thoracic aorta, in response to sulfur dioxide (SO2) derivatives “1:3 M/M sodium bisulfite (NaHSO3) and sodium sulfite (Na2SO3)” using PowerLab tissue bath system. Endothelial denudation enhanced relaxation responses of SO2 derivatives with an IC50 of 6.11 mM as compared to control rings with an IC50 of 6.21 mM, as well as the maximum relaxation (Emax) was increased from 62.026% ± 6.527% to 83.13% ± 14.755%. Furthermore, the relaxation responses to SO2 derivatives in aortic rings were significantly enhanced by indomethacin, clotrimazole and methylene blue with IC50’s of 4.8 mM, 5.33 mM and 4.01 mM, and Emax were raised to 101.1% ± 6.537%, 66.92 ± 7.538 and 104.68 ± 3.575, respectively. Meanwhile, L-NAME did not alter dose-dependent relaxation of SO2 derivatives in comparison to control aortic rings. The results of this study had shown that endothelium denudation and blocking of endothelium derived-relaxation factors enhanced vasodilator effect of SO2; this may clarify the role of endothelium in the vasodilatory mechanism of SO2.

Elevated levels of procoagulant microparticles in a patient with myocardial infarction, antiphospholipid antibodies and multifocal cardiac thrombosis
O Morel, L Jesel, JM Freyssinet, F Toti
Thrombosis Journal , 2005, DOI: 10.1186/1477-9560-3-15
Abstract: In primary anti-phospholipid syndrome (APS), arterial or venous thrombosis and recurrent pregnancy loss are common thrombotic manifestations associated with anti-phophospholipid antibodies (APL) [1]. A variety of cardiac affections including valvular lesions, myocardial dysfunction or infarction, early bypass graft failure, and intracardiac thrombosis have been reported [2-4]. Yet in vitro, APL inhibit phospholipid-dependent blood coagulation and bind to membrane phospholipids exposed by stimulated or apoptotic cells [5]. Furthermore, in the presence of APL, vascular cells are stimulated and acquire procoagulant, proadhesive and proinflammatory phenotypes [1,6]. Two non-exclusive hypotheses have been proposed to explain the thrombotic propensity in APS (i) APL could impede the natural anticoagulant protein C pathway, also involving anionic phospholipids (ii) APL would promote sustained cell activation through the interaction of immune complexes with vascular cells [1,7].Procoagulant microparticles (MP) are shed from the plasma membrane of any stimulated or apoptotic cells [8,9]. Under most physiopathological conditions among which acute myocardial syndrome, circulating MP, are mainly of platelet origin [10,11] and can be viewed as a "storage pool" by themselves, disseminating procoagulant activities [9,12]. In blood flow, released MP contribute to thrombotic propensity by virtue of exposed anionic phospholipids enhancing the catalytic surface available for blood coagulation. In addition, harbored membrane glycoproteins or antigens cytoadhesins, and proinflammatory lipids confer to MP the potency of cellular effectors through multiple amplification loops [13].Elevated levels of circulating MP were detected in various diseases, a proportion of them associated with thrombotic disorders [6,8,14-18]. In a particular patient with a past history of mesenteric vein thrombosis and moderate titers of anti-phospholipid antibodies referring for acute myocardial infarction, we h
Rol de la heterogeneidad endotelial en la regulación de la Hemostasia
Acta bioqu?-mica cl?-nica latinoamericana , 2006,
Abstract: the endothelium is an organ that is involved in several physiological processes, mainly blood fluid preservation. non-activated endothelial cells express an anticoagulant, antiadhesive and vasodilative phenotype, whereas activated endothelial cells express procoagulant, proadhesive and vasoconstrictive properties. the structure and function are regulated in space and time and this fact originates a specific vascular bed haemostasis . the objective of this work is to review the new concepts in endothelial cell heterogeneity and their influence in haemostasis regulation.
Evaluación de disfunción endotelial en pacientes con diabetes tipo 2
Velarde,María Susana; Prado,María Mercedes; Carrizo,Teresita del Rosario; Abregú,Adela Victoria; Sánchez,Sara Serafina;
Acta bioqu?-mica cl?-nica latinoamericana , 2007,
Abstract: the object of this work was to study molecules involved in endothelial activation, such as e-selectin (se-s) and the vasoconstrictor peptide endothelin-1 (et-1) in type 2 diabetes patients, and their relation with other cardiovascular risk factors. sixty-two patients with diabetes were compared with matched controls. se-s and et-1 concentrations in diabetes patients were significantly elevated compared with controls (se-s: 90.6±26.2 ng/ml vs 49.5±9.2 ng/ml, p<0.00001; et-1: 11.3±3.7 vs 7.7±0.5 pg/ml, p<0.001, respectively). se-s and et-1 levels in diabetes patients with normal and increased body mass index showed significant differences (se-s: 75.5±22.4 vs. 97.1±32.9 ng/ml, p<0.05; et-1: 8.4±2.4 vs. 14.1±4.9 pg/ml, p=0.001 respectively). there were no significant differences in none of the molecules values between patients with or without hypertension, smokers or non-smokers, neither in diabetes patients with or without hypercholesterolemia. eighty-one percent of the population with diabetes presented a poor glycemic control (ha1c>7%) and in these patients, et-1 plasma levels were significantly increased (p<0.01), but not se-s (p=0.74). these results show that obesity and a poor glycemic control increase the endothelial dysfunction in type 2 diabetes patients.
Fun??o endotelial de adolescentes normotensos sem fatores de risco para hipertens?o arterial
Andrade, Zélia M. de;Carvalhaes, Jo?o T. A.;Taddei, José A. A. C.;Christofalo, Dejaldo M. J.;Ajzen, Sergio A.;
Jornal de Pediatria , 2005, DOI: 10.2223/1377
Abstract: objective: to define standards for normal endothelial function in adolescents by high-resolution ultrasound measurement of endothelium-dependent vascular dilatation. methods: this was a cross-sectional, descriptive, observational study and part of the thematic project "clinical study of growth, behavior, arterial hypertension, obesity and oral health" (eccchos) that was developed by the discipline of nutrition at the universidade federal de s?o paulo. thirty-one adolescents, eight male and 23 female, with no risk factors for systemic arterial hypertension were selected from 1,420 high school students. the students were daytime pupils at a school in the southeastern district of the city of s?o paulo, the capital of s?o paulo state, located in the southeast region of brazil. all results are presented in the form of means with standard deviations and percentiles. results: for male students, endothelium-dependant dilation 90 seconds after the cuff was released was 20.9±6,7% [mean ±1 standard deviation] with a 10th percentile of 12.5 and for females these figures were 18.8±12.9% with a 10th percentile of 6.6%. values for the whole group of subjects were 19.3±11.7% and 6.7%, respectively. conclusion: endothelium-dependant vascular dilation of 6.7%, after 90 seconds, which corresponds to the 10th percentile, can be considered the lower limit of normality for this age group. knowledge of this limit is important for the diagnosis of endothelium dysfunction that appears before cardiovascular disease.
Marcadores de inflamación y disfunción endotelial en ni?os con diabetes tipo 1
Velarde,María S.; Carrizo,Teresita del R.; Prado,María M.; Díaz,Elba I.; Fonio,María C.; Bazán,María C.; Abregú,Adela V.;
Medicina (Buenos Aires) , 2010,
Abstract: a subclinical inflammation state was detected in the early step of diabetes, which increases the serum levels of cytokines that induce acute-phase protein synthesis as c-reactive protein (pcr) and fibrinogen (fg), stimulating the endothelial disfunction of adhesion molecules. thirty patients (15 boys, 15 girls) with type 1 diabetes (dt1), without vascular complications, were studied. their mean age and duration of diabetes were 11.8 ± 2.1 and 3.9 ± 3.2 years, respectively. the laboratory parameters evaluated were: blood leukocytes count, globular sedimentation velocity, fasting glycemia, glycosylated hemoglobin (hba1c), high sensitivity pcr (upcr), plasma soluble e-selectin (se-s), svcam-1 and microalbuminuria. increased levels of upcr, se-s and vcam-1 were found, compared with the control group control [0.60 (0.30-1.25) vs. 0.20 (0.20-0.65) mg/l, p = 0.013], [108 (60- 150) vs. 68 (56-82) ng/ml, p = 0.0031] y [750 (708-826) vs. 721 (674-751) ng/ml, p = 0.039] respectively. when diabetic patients were grouped according to duration of disease (= 3 and > de 3 years), upcr values were higher in the second group. upcr levels were better correlated with se-s (r = 0.44, p = 0.03) and vcam-1 (r = 0.49, p = 0.02). these results suggest the presence of pro-inflammatory and endothelial activation states, which are strongly associated with dt1.
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