Effects of enalapril and losartan on circulating adhesion molecules and monocyte chemotactic protein-1

2002 ◽  
Vol 103 (2) ◽  
pp. 131-136 ◽  
Author(s):  
B. JILMA ◽  
F.L. LI-SAW-HEE ◽  
O.F. WAGNER ◽  
D.G. BEEVERS ◽  
G.Y.H. LIP
Keyword(s):  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Converting Enzyme Inhibitors ◽  
Monocyte Chemotactic Protein ◽  
Chemotactic Protein

At least four independent studies in different clinical settings showed that angiotensin-converting enzyme inhibitors (ACE-Is) such as enalapril effectively decrease plasma levels of circulating adhesion molecules (cAMs). To examine whether this effect may be mediated by the decreased action of angiotensin, we compared the effects of enalapril with the direct angiotensin-II antagonist, losartan, on plasma levels of cAMs, and monocyte chemotactic protein-1 (MCP-1). In a randomized trial, we recruited 32 untreated patients (19 male, aged 59±13years) with hypertension, who received either enalapril (mean dose 17mg/day) or losartan (mean dose 77mg/day) at equipotent doses. Enalapril decreased plasma levels of all cAMs after 8weeks of treatment: cE-selectin levels decreased by 13% (P = 0.007), intercellular adhesion molecule-1 (cICAM-1) by 15% (P = 0.002) and vascular cell adhesion molecule-1 (cVCAM-1) by 19% (P = 0.003). Similarly, enalapril decreased plasma levels of MCP-1 by 13% (P<0.001). Losartan did not significantly change cAM or MCP-1 plasma concentrations after 8weeks of treatment: cE-selectin levels decreased by 3%, cICAM-1 by 5%, cVCAM-1 by 8%, whereas MCP-1 increased by 2% (all P = NS; not significant). The enalapril effect on percentage changes of cVCAM-1 was significantly different from losartan (P = 0.0429). Eight weeks of antihypertensive treatment with enalapril but not losartan, significantly decreased plasma levels of cAMs and MCP-1 in hypertensive patients. The beneficial effects of ACE-Is on cAMs may have implications for atherogenesis and the reduction of cardiovascular events, which cannot be fully explained by their antihypertensive effects alone.

Effects of progressive and maximal exercise on plasma levels of adhesion molecules in athletes with sickle cell trait with or without α-thalassemia

2007 ◽  
Vol 102 (1) ◽  
pp. 169-173 ◽  
Author(s):  
Geraldine Monchanin ◽  
Laura D. Serpero ◽  
Philippe Connes ◽  
Julien Tripette ◽  
Dieudonné Wouassi ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Sickle Cell ◽  
Adhesion Molecule ◽  
Plasma Levels ◽  
Sickle Cell Trait ◽  
Recovery Period ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Basal Plasma ◽  
Microcirculatory Disturbances

The aim of the study was to examine the effects of exercise on soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in sickle cell trait (SCT) athletes with or without α-thalassemia. Six athletes with SCT, seven athletes with both SCT and α-thalassemia (SCTAT), and seven control athletes (Cont) performed an incremental and maximal test on cycloergometer. Levels of sICAM-1 and sVCAM-1 were assessed at rest, immediately after the end of exercise, and 1, 2, and 24 h after exercise. Although Cont and SCTAT groups exhibited similar basal plasma levels of inflammatory and adhesion molecules, the SCT group had higher sVCAM-1 basal concentrations. Incremental exercise resulted in a significant increase of sVCAM-1 in all subjects, which remained elevated only in the SCT group during the recovery period. In conclusion, as sVCAM-1 increased with exercise and during the recovery period, our findings support the concept that SCT athletes might be at risk for microcirculatory disturbances and adhesive phenomena developing at rest and several hours after exercise. α-Thalassemia might be considered protective among exercising SCT subjects.

Levels of adhesion molecules do not decrease after 3 months of statin therapy in moderate hypercholesterolaemia

2003 ◽  
Vol 104 (2) ◽  
pp. 189-193 ◽  
Author(s):  
Bernd JILMA ◽  
Christian JOUKHADAR ◽  
Ulla DERHASCHNIG ◽  
Fausi RASSOUL ◽  
Volker RICHTER ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Plasma Levels ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Protein Levels ◽  
Cholesterol Levels ◽  
Before And After

Studies in animals and humans indicate a pivotal role for adhesion molecules (AMs) in the pathogenesis of atherosclerosis. Whereas an association between hypercholesterolaemia and AM expression has been suggested, it is unclear whether lowering cholesterol decreases AM expression and release. We compared the effects of a 3-month treatment with standard doses of three different statins (atorvastatin, simvastatin and pravastatin) on plasma levels of circulating AM (cAM) in 75 hypercholesterolaemic patients in a randomized clinical trial. Plasma levels of circulating (c)E-selectin, circulating intercellular adhesion molecule-1 (cICAM-1) and circulating vascular cell adhesion molecule-1 (cVCAM-1) were measured before and after 3 months of therapy. None of the statins lowered plasma cAM levels and pooled analyses of all patients showed a 1.7% [95% confidence interval (CI), -1.4–4.9%] increase in cE-selectin, a 2.1% (95% CI, -0.2–4.4%) increase in cICAM-1, and a 2.7% (95% CI, -0.6–6.1%) increase in cVCAM-1 levels. cAM levels did not decrease, even in patients with a >50% decrease (n = 19) in low-density lipoprotein cholesterol levels. This study provides strong evidence that 3 months of therapy with three different statins does not decrease cAM levels, despite normalization of cholesterol levels, and a minor decrease in C-reactive protein levels in patients with moderate hypercholesterolaemia.

Changes in leucocyte counts and soluble intercellular adhesion molecule-1 and E-selectin during cardiopulmonary bypass in children

Perfusion ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 322-327 ◽  
Author(s):  
Hilary J Williams ◽  
Naomi Rebuck ◽  
Martin J Elliott ◽  
Adam Finn
Keyword(s):  
Cardiopulmonary Bypass ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Plasma Concentrations ◽  
Endothelial Damage ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Soluble Adhesion Molecules ◽  
Cell Counts

A consequence of cardiopulmonary bypass (CPB) in young children is postoperative capillary leak and associated pulmonary dysfunction. Neutrophils sequester in the lungs and may contribute to functional endothelial damage. The endothelial adhesion molecules, E-selectin and intercellular adhesion molecule-1 (ICAM-1), mediate sequential steps in adhesion by binding to leucocyte ligands. Circulating forms of these proteins have been identified. We studied changes in the plasma concentrations of soluble E-selectin and soluble ICAM-1 using fixed phase immunoassays, and associated leucocyte counts in 10 paediatric patients undergoing CPB. Concentrations of soluble L-selectin and soluble ICAM-1 consistently fell during CPB from preoperative levels of 89 ± 17 ng/ml (mean ± 2SEM) and 218 + 61 ng/ml, respectively, to 39 ± 7 ng/ml and 84 ± 24 ng/ml, respectively at the beginning of maximum hypothermia. The haemodilution that occurred during CPB largely explained this fall, but not the more marked decrease in white cell counts that also occurred over this period (6.7 ± 1.1 to 1.7 ± 0.5 × 109/l) which may reflect increased leucocyte sequestration. By 24 h postoperatively, levels of both soluble adhesion molecules approached preoperative concentrations, as did lymphocyte counts. In marked contrast, neutrophil counts rose appreciably towards the end of CPB, and continued to rise to a maximum of 10.9 ± 3.1 ×109/l during the immediate postoperative period and remained at these elevated levels 24 h later. Major consistent changes in circulating leucocyte numbers which occur early in cardiopulmonary bypass may reflect changes in adhesion to the endothelium and consequent sequestration. Alterations in the levels of soluble adhesion proteins may influence these processes.

High Levels of Adhesion Molecules Are Associated with Impaired Endothelium-dependent Vasodilation in Patients with Peripheral Arterial Disease

2001 ◽  
Vol 85 (01) ◽  
pp. 63-66 ◽  
Author(s):  
Vincenzo Martone ◽  
Tiziana de Cristofaro ◽  
Salvatore Corrado ◽  
Antonio Silvestro ◽  
Anna Maria Di Donato ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Close Association ◽  
Plasma Concentrations ◽  
Arterial Disease ◽  
Cellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Cellular Adhesion Molecule

SummarySoluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1) were measured alongside flow-mediated vasodilation (FMD) in 34 patients with intermittent claudication and 14 control subjects. Patients with plasma sICAM-1 >253 ng/mL (median value) showed lower FMD than those with sICAM-1 <253 ng/mL (5.6 ± 1.8% vs 9.6 ± 4.2%, p <0.01). Similarly, in the 17 patients with plasma sVCAM-1 >414 ng/mL, FMD was lower than in the remaining 17 patients (6.1 ± 1.9% vs 9.2 ± 4.5%, p <0.05). Additionally, when endothelial dysfunction was defined as FMD ≤5.5%, patients with FMD below this value had higher plasma concentrations of sICAM-1 and sVCAM-1 than those with FMD >5.5%. Therefore, our findings indicate a close association between elevated plasma levels of adhesion molecules and endothelial dysfunction. As impaired endothelial function is one of the first steps in atherogenesis, our findings have clinical relevance since they serve as the basis for further evaluation of sICAM-1 and sVCAM-1 as potential plasma markers for progression of atherosclerosis in a population at high risk.

scholarly journals Adhesion-dependent interactions between eosinophils and cholinergic nerves

2002 ◽  
Vol 282 (6) ◽  
pp. L1229-L1238 ◽  
Author(s):  
Paul J. Kingham ◽  
W. Graham McLean ◽  
Deborah A. Sawatzky ◽  
Marie Therese Walsh ◽  
Richard W. Costello
Keyword(s):  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Function ◽  
Intercellular Adhesion Molecule ◽  
Cholinergic Nerves ◽  
Intercellular Adhesion Molecule 1 ◽  
Parasympathetic Nerves ◽  
Oxidase Inhibition ◽  
Cell Adhesion Molecule 1 ◽  
Eosinophil Degranulation

Eosinophils adhere to airway cholinergic nerves and influence nerve cell function by releasing granule proteins onto inhibitory neuronal M2 muscarinic receptors. This study investigated the mechanism of eosinophil degranulation by cholinergic nerves. Eosinophils were cocultured with IMR32 cholinergic nerve cells, and eosinophil peroxidase (EPO) or leukotriene C4 (LTC4) release was measured. Coculture of eosinophils with nerves significantly increased EPO and LTC4 release compared with eosinophils alone. IMR32 cells, like parasympathetic nerves, express the adhesion molecules vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 (ICAM-1). Inhibition of these adhesion molecules alone or in combination significantly inhibited eosinophil degranulation. IMR32 cells also significantly augmented the eosinophil degranulation produced by formyl-Met-Leu-Phe. Eosinophil adhesion to IMR32 cells resulted in an ICAM-1-mediated production of reactive oxygen species via a neuronal NADPH oxidase, inhibition of which significantly inhibited eosinophil degranulation. Additionally, eosinophil adhesion increased the release of ACh from IMR32 cells. These neuroinflammatory cell interactions may be relevant in a variety of inflammatory and neurological conditions.

scholarly journals Distinct Roles For ROCK1 and ROCK2 in the Regulation of Oxldl-Mediated Endothelial Dysfunction

2018 ◽  
Vol 49 (2) ◽  
pp. 565-577 ◽  
Author(s):  
Lei Huang ◽  
Fan Dai ◽  
Lian Tang ◽  
Xiaofeng Bao ◽  
Zhaoguo Liu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Dysfunction ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Apoptosis ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Rock Inhibitor ◽  
Vimentin Expression

Background/Aims: This study used Rho-associated protein kinase (ROCK) isoform-selective suppression or a ROCK inhibitor to analyze the roles of ROCK1 and ROCK2 in regulating endothelial dysfunction triggered by oxidized low-density lipoprotein (oxLDL). Methods: ROCK1 or ROCK2 expression in human umbilical vein endothelial cells (HUVECs) was suppressed by small interfering RNA (siRNA). HUVECs were pretreated with 30 μM Y27632 (pan ROCK inhibitor) for 30 min before exposure to 200 μg/mL oxLDL for an additional 24 h. Cell viability was determined by the MTT assay, and cell apoptosis was evaluated by the TUNEL assay. Protein expression and phosphorylation were assessed by Western blot analysis. The morphology of total and phosphorylated vimentin (p-vimentin) and the co-localization of vimentin with vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) were detected by the immunofluorescence assay. The adhesion of promonocytic U937 cells to HUVECs was observed by light microscopy. Results: ROCK2 suppression or Y27632 treatment, rather than ROCK1 deletion, effectively reduced endothelial cell apoptosis and preserved cell survival. ROCK2 suppression exhibited improved vimentin and p-vimentin cytoskeleton stability and decreased vimentin cleavage by attenuating caspase-3 activity. In addition, increased p-vimentin expression induced by oxLDL was significantly inhibited by ROCK2 deletion or Y27632 treatment. In contrast, ROCK1 suppression showed no obvious effects on the vimentin cytoskeleton, but significantly regulated the expression of adhesion molecules. Endothelial ICAM-1 or VCAM-1 expression induced by oxLDL was obviously inhibited by ROCK1 suppression or Y27632 treatment. Moreover, the expression of ICAM-1 induced by oxLDL could also be reduced by ROCK2 suppression. Furthermore, ROCK2 deficiency or Y27632 treatment inhibited the redistribution of adhesion molecules and their co-localization with vimentin caused by oxLDL. These effects resulted in the significant inhibition of monocyte-endothelial adhesion induced by oxLDL. Conclusion: The results of this study support the novel concept that ROCK1 is involved in oxLDL-induced cell adhesion by regulating adhesion molecule expression, whereas ROCK2 is required for both endothelial apoptosis and adhesion by regulating both the vimentin cytoskeleton and adhesion molecules. Consequently, ROCK1 and ROCK2 have distinct roles in the regulation of oxLDL-mediated endothelial dysfunction.

Sign in / Sign up

Export Citation Format

Share Document