Pub Date : 2001-01-01DOI: 10.1080/10623320109051565
M. Maragoudakis, Nancy Kraniti, Eleptheria Giannopoulou, K. Alexopoulos, J. Matsoukas
The angiogenic action of thrombin has been shown to be mediated by activation of the thrombin receptor. In this report we studied the effects of SFLLR, an agonist of the activated thrombin receptor and thrombin receptor peptide and non peptide antagonists on angiogenesis in the chick chorioallantoic membrane (CAM) system. As antagonists were used the tripeptide FPR and non-peptide 1,4-disubstituted piperazine derivatives. The pentapeptide SFLLR, like thrombin, caused a marked stimulation of angiogenesis in the CAM. FPR and the piperazine derivatives caused suppression of angiogenesis and in combination with thrombin antagonized its angiogenic effect. Thrombin and SFLLR activated progelatinase A (MMP-2) in the culture medium of human umbilical cord endothelial cells (HUVECs). MMP-2 is involved in the early steps of angiogenesis leading to local dissolution of basement membrane collagen and migration of the activated endothelial cells. FPR and the piperazine derivatives inhibited the activation of this enzyme. They also antagonised the effects of both thrombin and SFLLR on MMP-2 activation. These results suggest that non-thrombogenic agonists or antagonists of the activated thrombin receptor can be used as modulators of angiogenesis.
{"title":"Modulation of angiogenesis and progelatinase a by thrombin receptor mimetics and antagonists.","authors":"M. Maragoudakis, Nancy Kraniti, Eleptheria Giannopoulou, K. Alexopoulos, J. Matsoukas","doi":"10.1080/10623320109051565","DOIUrl":"https://doi.org/10.1080/10623320109051565","url":null,"abstract":"The angiogenic action of thrombin has been shown to be mediated by activation of the thrombin receptor. In this report we studied the effects of SFLLR, an agonist of the activated thrombin receptor and thrombin receptor peptide and non peptide antagonists on angiogenesis in the chick chorioallantoic membrane (CAM) system. As antagonists were used the tripeptide FPR and non-peptide 1,4-disubstituted piperazine derivatives. The pentapeptide SFLLR, like thrombin, caused a marked stimulation of angiogenesis in the CAM. FPR and the piperazine derivatives caused suppression of angiogenesis and in combination with thrombin antagonized its angiogenic effect. Thrombin and SFLLR activated progelatinase A (MMP-2) in the culture medium of human umbilical cord endothelial cells (HUVECs). MMP-2 is involved in the early steps of angiogenesis leading to local dissolution of basement membrane collagen and migration of the activated endothelial cells. FPR and the piperazine derivatives inhibited the activation of this enzyme. They also antagonised the effects of both thrombin and SFLLR on MMP-2 activation. These results suggest that non-thrombogenic agonists or antagonists of the activated thrombin receptor can be used as modulators of angiogenesis.","PeriodicalId":11588,"journal":{"name":"Endothelium-journal of Endothelial Cell Research","volume":"8 1","pages":"195-205"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74736239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.3109/10623320109090800
G. Rinaldi
Several maneuvers usually employed to set up isolated vascular preparations could effect the endothelium-dependent relaxation (EDR). The effects of five such maneuvers were studied in rings of rat aorta: 1) Type of anesthesia, 2) Cold storage of the vessels, 3) Length of the stabilization period, 4) Repeated contractions during stabilization, and 5) Performance of washouts during stabilization. Repeated contractions with norepinephrine (NE) 0.1 microM after stabilization altered neither the contraction nor the EDR induced by acetylcholine (Ach) 1 microM. Pentobarbital anesthesia and cold storage of the preparations for 24 h significantly decreased the EDR without effecting the contractile response of the rings. The absence of washouts during stabilization increased the contractions to either NE 0.1 microM or KCl 80 mM by nearly 50%. This increase was prevented by endothelial disruption or, in the presence of intact endothelium, by repeated washouts or by incubation with Bosentan 22 microM. It is concluded that 1) Anesthesia of the animals and cold storage of the preparations can alter the EDR even in the absence of contractile changes in the smooth muscle, and 2) Accumulation of endothelin during the incubation period, even if not producing changes in the resting tension, can substantially alter the subsequent response to vasoactive interventions.
{"title":"Influence of several methodological procedures utilized to obtain in vitro vascular preparations on endothelial activity.","authors":"G. Rinaldi","doi":"10.3109/10623320109090800","DOIUrl":"https://doi.org/10.3109/10623320109090800","url":null,"abstract":"Several maneuvers usually employed to set up isolated vascular preparations could effect the endothelium-dependent relaxation (EDR). The effects of five such maneuvers were studied in rings of rat aorta: 1) Type of anesthesia, 2) Cold storage of the vessels, 3) Length of the stabilization period, 4) Repeated contractions during stabilization, and 5) Performance of washouts during stabilization. Repeated contractions with norepinephrine (NE) 0.1 microM after stabilization altered neither the contraction nor the EDR induced by acetylcholine (Ach) 1 microM. Pentobarbital anesthesia and cold storage of the preparations for 24 h significantly decreased the EDR without effecting the contractile response of the rings. The absence of washouts during stabilization increased the contractions to either NE 0.1 microM or KCl 80 mM by nearly 50%. This increase was prevented by endothelial disruption or, in the presence of intact endothelium, by repeated washouts or by incubation with Bosentan 22 microM. It is concluded that 1) Anesthesia of the animals and cold storage of the preparations can alter the EDR even in the absence of contractile changes in the smooth muscle, and 2) Accumulation of endothelin during the incubation period, even if not producing changes in the resting tension, can substantially alter the subsequent response to vasoactive interventions.","PeriodicalId":11588,"journal":{"name":"Endothelium-journal of Endothelial Cell Research","volume":"5 1","pages":"235-42"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88937861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.3109/10623320109090807
I. Blasig, H. Bauer, R. Haseloff
{"title":"Conference Report: Third Symposium: Signal Transduction in the Blood-Brain Barrier September 22–24, 2000, Potsdam, Germany","authors":"I. Blasig, H. Bauer, R. Haseloff","doi":"10.3109/10623320109090807","DOIUrl":"https://doi.org/10.3109/10623320109090807","url":null,"abstract":"","PeriodicalId":11588,"journal":{"name":"Endothelium-journal of Endothelial Cell Research","volume":"10 1","pages":"293-310"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73580081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.3109/10623320109063155
R. Mcdouall, Mark W. Farrar, Shabeena Khan, Magdi H. Yacoub, Sean P. Allen
The expression of adhesion molecules by endothelial cells is crucial in many inflammatory processes and plays an active role in the development of reperfusion injury, acute and chronic rejection. The expression of adhesion molecules in different parts of the coronary tree to cytokine stimulation is not known. We describe here a detailed study of the effects of the inflammatory cytokines TNFalpha and IL-1beta on the expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intracellular cell adhesion molecule-1 (ICAM-1) on human aortic root (HAEC), coronary artery (HCAEC) and heart microvascular (HHMEC)) endothelial cells in culture, using flow cytometry. We found constitutive levels of both VCAM-1 and E-Selectin on HCAEC and HHMEC (approximately 20%) which were significantly higher compared to HAEC (approximately 3%). There was an extreme sensitivity of HCAEC and HHMEC to 0.002 ng/ml TNFalpha: (VCAM-1 approximately 40%, E-Selectin approximately 25%) respectively, compared to HAEC (VCAM-1 approximately 5%, E-selectin approximately 5%). IL-1beta showed a similar pattern of expression at low doses (5 U/ml), but was less potent. We also observed prolonged expression of these adhesion molecules, especially on the HHMEC (>48 hours) compared to HAEC. There was also increased binding of peripheral blood mononuclear cells (PBMC) to both non-stimulated and TNFalpha stimulated HCAEC and HHMEC compared to HAEC. This data suggest that endothelial cells in different regions of the coronary tree express different patterns of basal and cytokine-stimulated adhesion molecule expression.
{"title":"Unique sensitivities to cytokine regulated expression of adhesion molecules in human heart-derived endothelial cells.","authors":"R. Mcdouall, Mark W. Farrar, Shabeena Khan, Magdi H. Yacoub, Sean P. Allen","doi":"10.3109/10623320109063155","DOIUrl":"https://doi.org/10.3109/10623320109063155","url":null,"abstract":"The expression of adhesion molecules by endothelial cells is crucial in many inflammatory processes and plays an active role in the development of reperfusion injury, acute and chronic rejection. The expression of adhesion molecules in different parts of the coronary tree to cytokine stimulation is not known. We describe here a detailed study of the effects of the inflammatory cytokines TNFalpha and IL-1beta on the expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intracellular cell adhesion molecule-1 (ICAM-1) on human aortic root (HAEC), coronary artery (HCAEC) and heart microvascular (HHMEC)) endothelial cells in culture, using flow cytometry. We found constitutive levels of both VCAM-1 and E-Selectin on HCAEC and HHMEC (approximately 20%) which were significantly higher compared to HAEC (approximately 3%). There was an extreme sensitivity of HCAEC and HHMEC to 0.002 ng/ml TNFalpha: (VCAM-1 approximately 40%, E-Selectin approximately 25%) respectively, compared to HAEC (VCAM-1 approximately 5%, E-selectin approximately 5%). IL-1beta showed a similar pattern of expression at low doses (5 U/ml), but was less potent. We also observed prolonged expression of these adhesion molecules, especially on the HHMEC (>48 hours) compared to HAEC. There was also increased binding of peripheral blood mononuclear cells (PBMC) to both non-stimulated and TNFalpha stimulated HCAEC and HHMEC compared to HAEC. This data suggest that endothelial cells in different regions of the coronary tree express different patterns of basal and cytokine-stimulated adhesion molecule expression.","PeriodicalId":11588,"journal":{"name":"Endothelium-journal of Endothelial Cell Research","volume":"30 1","pages":"25-40"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74027578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1080/10623320109051567
N. Akhta, S. Carlso, A. Pesarini, N. Ambulos, A. Passaniti
To isolate matrix molecules with angiogenic activity, tumor extracellular matrix (ECM) fractions from the basement membrane preparation Matrigel were analyzed for effects on endothelial cell (EC) proliferation, differentiation, and vessel formation in vivo. Inhibition of human and bovine EC DNA synthesis was evident upon treatment with several soluble Matrigel fractions including conditioned media (MGCM). After size fractionation of MGCM, EC growth arrest was activated by factor(s) smaller than 3,000 daltons (3KF). Bovine EC differentiation (tube formation) was promoted by both MGCM and 3KF fractions in two different models using matrigel or collagen gels to stimulate tube formation. The 3KF factor(s) stimulated angiogenesis when implanted in the cornea or subcutaneously in mice. FGF-induced angiogenesis and blood flow were increased in the presence of 3KF factor(s), an effect that was inhibited by the anti-angiogenic molecule endostatin. Further characterization of the low molecular weight 3KF samples by RP-HPLC revealed several fractions exhibiting EC growth arrest activity. These results suggest that the ability of ECM preparations to induce EC growth arrest and tube formation may reside, at least partially, in previously undetected low molecular weight molecules. Characterization of these ECM-associated inhibitors may lead to the development of novel anti-angiogenic and anti-tumor compounds.
{"title":"Extracellular matrix-derived angiogenic factor(s) inhibit endothelial cell proliferation, enhance differentiation, and stimulate angiogenesis in vivo.","authors":"N. Akhta, S. Carlso, A. Pesarini, N. Ambulos, A. Passaniti","doi":"10.1080/10623320109051567","DOIUrl":"https://doi.org/10.1080/10623320109051567","url":null,"abstract":"To isolate matrix molecules with angiogenic activity, tumor extracellular matrix (ECM) fractions from the basement membrane preparation Matrigel were analyzed for effects on endothelial cell (EC) proliferation, differentiation, and vessel formation in vivo. Inhibition of human and bovine EC DNA synthesis was evident upon treatment with several soluble Matrigel fractions including conditioned media (MGCM). After size fractionation of MGCM, EC growth arrest was activated by factor(s) smaller than 3,000 daltons (3KF). Bovine EC differentiation (tube formation) was promoted by both MGCM and 3KF fractions in two different models using matrigel or collagen gels to stimulate tube formation. The 3KF factor(s) stimulated angiogenesis when implanted in the cornea or subcutaneously in mice. FGF-induced angiogenesis and blood flow were increased in the presence of 3KF factor(s), an effect that was inhibited by the anti-angiogenic molecule endostatin. Further characterization of the low molecular weight 3KF samples by RP-HPLC revealed several fractions exhibiting EC growth arrest activity. These results suggest that the ability of ECM preparations to induce EC growth arrest and tube formation may reside, at least partially, in previously undetected low molecular weight molecules. Characterization of these ECM-associated inhibitors may lead to the development of novel anti-angiogenic and anti-tumor compounds.","PeriodicalId":11588,"journal":{"name":"Endothelium-journal of Endothelial Cell Research","volume":"34 1","pages":"221-34"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79136489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.3109/10623320109165322
D. Antoniucci, V. Miller, G. Sieck, L. Fitzpatrick
Endothelin-1 is an endothelium-derived factor which alters tone and proliferation of vascular smooth muscle and has been implicated in the development of atherosclerosis. Estrogen modulates production of and contractile responses to endothelin-1. Since atherosclerosis is less in estrogen-replete women compared to men, experiments were designed to determine whether or not there were gender-associated differences in proliferative responses to endothelin-1 and effect of estrogen status on those responses. Proliferation of smooth muscle cells derived from coronary arteries of sexually mature, gondally intact male and female and oophorectomized female pigs was determined by thymidine incorporation in the absence and presence of endothelin-1 with and without 17beta-estradiol. Endothelin-1 (10(-9) M to 10(-7) M) significantly inhibited proliferation only in coronary smooth muscle cells from intact female pigs. Addition of beta-estradiol inhibited proliferation of cells from intact females but there was not a synergistic effect with endothelin-1. Gender associated inhibition of smooth muscle proliferation by endothelin-1 may contribute, in part, to cardioprotection noted in estrogen-replete states.
{"title":"Gender-related differences in proliferative responses of vascular smooth muscle cells to endothelin-1.","authors":"D. Antoniucci, V. Miller, G. Sieck, L. Fitzpatrick","doi":"10.3109/10623320109165322","DOIUrl":"https://doi.org/10.3109/10623320109165322","url":null,"abstract":"Endothelin-1 is an endothelium-derived factor which alters tone and proliferation of vascular smooth muscle and has been implicated in the development of atherosclerosis. Estrogen modulates production of and contractile responses to endothelin-1. Since atherosclerosis is less in estrogen-replete women compared to men, experiments were designed to determine whether or not there were gender-associated differences in proliferative responses to endothelin-1 and effect of estrogen status on those responses. Proliferation of smooth muscle cells derived from coronary arteries of sexually mature, gondally intact male and female and oophorectomized female pigs was determined by thymidine incorporation in the absence and presence of endothelin-1 with and without 17beta-estradiol. Endothelin-1 (10(-9) M to 10(-7) M) significantly inhibited proliferation only in coronary smooth muscle cells from intact female pigs. Addition of beta-estradiol inhibited proliferation of cells from intact females but there was not a synergistic effect with endothelin-1. Gender associated inhibition of smooth muscle proliferation by endothelin-1 may contribute, in part, to cardioprotection noted in estrogen-replete states.","PeriodicalId":11588,"journal":{"name":"Endothelium-journal of Endothelial Cell Research","volume":"79 1","pages":"137-45"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80134806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.3109/10623320109165320
Christopher G. Kevil, Tadayuki Oshima, J. Steven Alexander
OBJECTIVE The purpose of this study was to determine the contribution of p38 MAP kinase activity during hydrogen peroxide mediated increased endothelial solute permeability. We also sought to identify the role of p38 MAP kinase-mediated changes in endothelial cell architecture due to hydrogen peroxide challenge. METHODS Hydrogen peroxide mediated permeability of HUVEC was determined with and without inhibition of p38 MAP kinase by SB202190. Hydrogen peroxide mediated rearrangement of the endothelial actin cytoskeleton and junctional proteins occludin and ZO-1 were observed by immunofluorescence microscopy. RESULTS Hydrogen peroxide treatment of endothelial monolayers caused a significant increase in solute permeability over a ninety-minute time period. Oxidant-mediated permeability and phosphorylation of p38 MAP kinase was significantly attenuated by SB 202190. Immunofluorescent staining for the tight junctional proteins occludin and ZO-1 demonstrated that oxidant challenge caused a loss of endothelial tight junction organization. Rhodamine phalloidin staining of the actin cytoskeleton showed that hydrogen peroxide stimulated increased stress fiber formation with concomitant gap formation between adjacent endothelial cells. Inhibition of p38 MAP kinase during oxidant challenge significantly attenuated actin stress fiber formation and prevented gap formation. CONCLUSIONS These data demonstrate that p38 MAP kinase activity is involved in hydrogen peroxide mediated permeability, stress fiber formation, and intracellular gap formation.
{"title":"The role of p38 MAP kinase in hydrogen peroxide mediated endothelial solute permeability.","authors":"Christopher G. Kevil, Tadayuki Oshima, J. Steven Alexander","doi":"10.3109/10623320109165320","DOIUrl":"https://doi.org/10.3109/10623320109165320","url":null,"abstract":"OBJECTIVE The purpose of this study was to determine the contribution of p38 MAP kinase activity during hydrogen peroxide mediated increased endothelial solute permeability. We also sought to identify the role of p38 MAP kinase-mediated changes in endothelial cell architecture due to hydrogen peroxide challenge. METHODS Hydrogen peroxide mediated permeability of HUVEC was determined with and without inhibition of p38 MAP kinase by SB202190. Hydrogen peroxide mediated rearrangement of the endothelial actin cytoskeleton and junctional proteins occludin and ZO-1 were observed by immunofluorescence microscopy. RESULTS Hydrogen peroxide treatment of endothelial monolayers caused a significant increase in solute permeability over a ninety-minute time period. Oxidant-mediated permeability and phosphorylation of p38 MAP kinase was significantly attenuated by SB 202190. Immunofluorescent staining for the tight junctional proteins occludin and ZO-1 demonstrated that oxidant challenge caused a loss of endothelial tight junction organization. Rhodamine phalloidin staining of the actin cytoskeleton showed that hydrogen peroxide stimulated increased stress fiber formation with concomitant gap formation between adjacent endothelial cells. Inhibition of p38 MAP kinase during oxidant challenge significantly attenuated actin stress fiber formation and prevented gap formation. CONCLUSIONS These data demonstrate that p38 MAP kinase activity is involved in hydrogen peroxide mediated permeability, stress fiber formation, and intracellular gap formation.","PeriodicalId":11588,"journal":{"name":"Endothelium-journal of Endothelial Cell Research","volume":"51 1","pages":"107-16"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84649635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.3109/10623320109165324
Jose Luis Accin, A. Sotomayor, Freddy Trujillo, J. Barrera, L. Bautista, Patrico López-Jaramillo
The endothelium plays a critical role in vascular homeostasis. Recently, a noninvasive method has been developed to assess flow mediated vasodilatation of the brachial artery (FMD). This test is remarkably stable overtime but no clear set of normal values has been developed. The purposes of our study were to evaluate the accuracy and reproducibility and to identify a set of normal values of FMD. We included 253 normotensive healthy volunteers from three Colombian cities (mean age: 38.2 years; 33% were women). All subjects underwent ultrasound evaluation of endothelial and smooth muscle function. Flow mediated vessel diameter change was measured by two independent observers. The interobserver Lin's concordance correlation coefficient was 0.88% (95% CI: 0.82, 0.94) and there was no evidence of systematic difference between the two measurements (mean difference of -0.30% with limits of agreement of -4.48 to 3.87). Mean %FMD was 11.98% (95% CI: 11.36, 12.61), 13.32% (95% CI: 12.39, 14.25) in women and 11.32% (95% CI: 10.52, 12.13) in men. Subjects with no cardiovascular risk factors had a mean %FMD of 13.74% (95% CI: 13.14, 14.35), in contrast to a mean of only 7.40% (95% CI: 4.33, 9.91) in those with at least one risk factor. A %FMD cut point of 10.4 had a sensitivity of 71.2% and an specificity of 77.2% to identify subjects with at least one cardiovascular risk factor. Using this cut point, endothelial dysfunction was 3.13 times more frequent in subjects with than in subjects without cardiovascular risk factors (95% CI: 2.30, 4.25). In addition, obesity, smoking and hypercholesterolemia were the modifiable risk factors with largest independent significant reduction effects on %FMD. FMD measurements can be made with high accuracy and precision, and a cut point of 10.4% is useful to discriminate between subjects with and without cardiovascular risk factors, and can be recommended as a screening test for the detection of patients at risk of CVD.
{"title":"Colombian study to assess the use of noninvasive determination of endothelium-mediated vasodilatation (CANDEV). Normal values and factors associated.","authors":"Jose Luis Accin, A. Sotomayor, Freddy Trujillo, J. Barrera, L. Bautista, Patrico López-Jaramillo","doi":"10.3109/10623320109165324","DOIUrl":"https://doi.org/10.3109/10623320109165324","url":null,"abstract":"The endothelium plays a critical role in vascular homeostasis. Recently, a noninvasive method has been developed to assess flow mediated vasodilatation of the brachial artery (FMD). This test is remarkably stable overtime but no clear set of normal values has been developed. The purposes of our study were to evaluate the accuracy and reproducibility and to identify a set of normal values of FMD. We included 253 normotensive healthy volunteers from three Colombian cities (mean age: 38.2 years; 33% were women). All subjects underwent ultrasound evaluation of endothelial and smooth muscle function. Flow mediated vessel diameter change was measured by two independent observers. The interobserver Lin's concordance correlation coefficient was 0.88% (95% CI: 0.82, 0.94) and there was no evidence of systematic difference between the two measurements (mean difference of -0.30% with limits of agreement of -4.48 to 3.87). Mean %FMD was 11.98% (95% CI: 11.36, 12.61), 13.32% (95% CI: 12.39, 14.25) in women and 11.32% (95% CI: 10.52, 12.13) in men. Subjects with no cardiovascular risk factors had a mean %FMD of 13.74% (95% CI: 13.14, 14.35), in contrast to a mean of only 7.40% (95% CI: 4.33, 9.91) in those with at least one risk factor. A %FMD cut point of 10.4 had a sensitivity of 71.2% and an specificity of 77.2% to identify subjects with at least one cardiovascular risk factor. Using this cut point, endothelial dysfunction was 3.13 times more frequent in subjects with than in subjects without cardiovascular risk factors (95% CI: 2.30, 4.25). In addition, obesity, smoking and hypercholesterolemia were the modifiable risk factors with largest independent significant reduction effects on %FMD. FMD measurements can be made with high accuracy and precision, and a cut point of 10.4% is useful to discriminate between subjects with and without cardiovascular risk factors, and can be recommended as a screening test for the detection of patients at risk of CVD.","PeriodicalId":11588,"journal":{"name":"Endothelium-journal of Endothelial Cell Research","volume":"76 1","pages":"157-66"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79267953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.3109/10623320109090804
A. Rebolledo, G. Rinaldi, V. Milesi, A. Gómez Alvis, A. O. Grassi de Gende
The effect of contractions elicited with ET1 and AVP after preincubating rat aortic and tail artery rings with a hyperinsulinemic dose (3 nM) of insulin were studied. Insulin preincubation (120 min), in the presence of 0.1 mM L-NAME, depressed contraction of aortic rings to 0.01 microM ET1 (132 +/- 6 vs. 161 +/- 9 mg/mm2 in control, n = 25; p < 0.05) and to 1 microM AVP (84 +/- 7 vs. 110 +/- 9 mg/mm2 in control, n = 16; p < 0.05), but did not modify 45Ca influx to the cell. Insulin-induced relaxation was inhibited by indomethacin 10 microM, an antagonist of prostaglandin synthesis, and also by blockade of insulin receptors with 30 microM genistein. A short insulin preincubation (15 min) did not modify ET1 contractions. In rat tail artery, insulin preincubation (120 min) increased the force developed by ET1 (847 +/- 45 vs. 596 +/- 99 mgF/mgW in controls, n = 14) by stimulating TXA2 release and/or actions. In summary, the present results suggest that endothelial factors are involved in both the vasoconstrictor and vasodilator effects of insulin on rat vessels.
研究了高胰岛素剂量(3 nM)胰岛素预孵育大鼠主动脉和尾动脉环后，ET1和AVP诱导的收缩作用。胰岛素预孵育(120分钟)，在0.1 mM L-NAME存在的情况下，将主动脉环收缩降至0.01微米ET1(对照组为132 +/- 6，对照组为161 +/- 9 mg/mm2, n = 25;p < 0.05)和1 μ m AVP(对照组为84 +/- 7，对照组为110 +/- 9 mg/mm2, n = 16;p < 0.05)，但不改变45Ca向细胞内流。吲哚美辛(一种前列腺素合成拮抗剂)可抑制胰岛素诱导的松弛，染料木素(30 microM)可阻断胰岛素受体。短胰岛素预孵育(15分钟)没有改变ET1收缩。在大鼠尾动脉中，胰岛素预培养(120分钟)通过刺激TXA2释放和/或作用，增加了ET1产生的力(对照组为847 +/- 45，对照组为596 +/- 99 mg /mgW, n = 14)。综上所述，目前的结果表明，内皮因子参与了胰岛素对大鼠血管的收缩和扩张作用。
{"title":"Insulin preincubation effects on rat vessel contractile responses: role of the endothelium.","authors":"A. Rebolledo, G. Rinaldi, V. Milesi, A. Gómez Alvis, A. O. Grassi de Gende","doi":"10.3109/10623320109090804","DOIUrl":"https://doi.org/10.3109/10623320109090804","url":null,"abstract":"The effect of contractions elicited with ET1 and AVP after preincubating rat aortic and tail artery rings with a hyperinsulinemic dose (3 nM) of insulin were studied. Insulin preincubation (120 min), in the presence of 0.1 mM L-NAME, depressed contraction of aortic rings to 0.01 microM ET1 (132 +/- 6 vs. 161 +/- 9 mg/mm2 in control, n = 25; p < 0.05) and to 1 microM AVP (84 +/- 7 vs. 110 +/- 9 mg/mm2 in control, n = 16; p < 0.05), but did not modify 45Ca influx to the cell. Insulin-induced relaxation was inhibited by indomethacin 10 microM, an antagonist of prostaglandin synthesis, and also by blockade of insulin receptors with 30 microM genistein. A short insulin preincubation (15 min) did not modify ET1 contractions. In rat tail artery, insulin preincubation (120 min) increased the force developed by ET1 (847 +/- 45 vs. 596 +/- 99 mgF/mgW in controls, n = 14) by stimulating TXA2 release and/or actions. In summary, the present results suggest that endothelial factors are involved in both the vasoconstrictor and vasodilator effects of insulin on rat vessels.","PeriodicalId":11588,"journal":{"name":"Endothelium-journal of Endothelial Cell Research","volume":"44 1","pages":"269-76"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88162058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.3109/10623320109063157
Burnatowska-Hledin, A. Zeneberg, A. Roulo, J. Grobe, P. Zhao, P. Lelkes, P. Clare, C. Barney
The vasopressin-activated calcium-mobilizing (VACM-1) protein is a unique arginine vasopressin (AVP) receptor which shares sequence homology with the cullins, genes involved in the regulation of cell cycle transitions. Unlike either cullins or AVP receptors, however, VACM-1 is expressed exclusively in the vascular endothelial cells and in the renal collecting tubule cells. In order to test the hypothesis that the expression of VACM-1 might be correlated with the cell cycle, and to establish an endothelial cell model for the VACM-1 receptor, we examined VACM-1 expression in rat adrenal medulla endothelial cells (RAMEC). Northern and Western blot analyses of mRNA and protein from RAMEC identified presence of 6.4 kb mRNA and a Mr 81 kDa protein, respectively. Immunostaining of RAMEC with anti-VACM-1 antibodies and Western blot analyses indicated that in RAMEC, VACM-1 protein expression is dependent on the cell cycle. VACM-1 protein virtually disappears during the S phase and localizes to the cytosol during cell division and to the cell membrane at the completion of cytokinesis. Furthermore, pretreatment of RAMEC with anti-VACM-1 specific antibodies increased basal levels of Ca2+and attenuated the AVP-dependent increase in cytosolic Ca2+. In summary, these results indicate that VACM-1 protein expression in RAMEC membrane is linked to the cell cycle, and consequently, VACM-1 may be involved in the regulation of cell division.
{"title":"Expression of VACM-1 protein in cultured rat adrenal endothelial cells is linked to the cell cycle.","authors":"Burnatowska-Hledin, A. Zeneberg, A. Roulo, J. Grobe, P. Zhao, P. Lelkes, P. Clare, C. Barney","doi":"10.3109/10623320109063157","DOIUrl":"https://doi.org/10.3109/10623320109063157","url":null,"abstract":"The vasopressin-activated calcium-mobilizing (VACM-1) protein is a unique arginine vasopressin (AVP) receptor which shares sequence homology with the cullins, genes involved in the regulation of cell cycle transitions. Unlike either cullins or AVP receptors, however, VACM-1 is expressed exclusively in the vascular endothelial cells and in the renal collecting tubule cells. In order to test the hypothesis that the expression of VACM-1 might be correlated with the cell cycle, and to establish an endothelial cell model for the VACM-1 receptor, we examined VACM-1 expression in rat adrenal medulla endothelial cells (RAMEC). Northern and Western blot analyses of mRNA and protein from RAMEC identified presence of 6.4 kb mRNA and a Mr 81 kDa protein, respectively. Immunostaining of RAMEC with anti-VACM-1 antibodies and Western blot analyses indicated that in RAMEC, VACM-1 protein expression is dependent on the cell cycle. VACM-1 protein virtually disappears during the S phase and localizes to the cytosol during cell division and to the cell membrane at the completion of cytokinesis. Furthermore, pretreatment of RAMEC with anti-VACM-1 specific antibodies increased basal levels of Ca2+and attenuated the AVP-dependent increase in cytosolic Ca2+. In summary, these results indicate that VACM-1 protein expression in RAMEC membrane is linked to the cell cycle, and consequently, VACM-1 may be involved in the regulation of cell division.","PeriodicalId":11588,"journal":{"name":"Endothelium-journal of Endothelial Cell Research","volume":"50 1","pages":"49-63"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78243213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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