Endothelin-1 Stimulates Small Artery VCAM-1 Expression through p38MAPK-Dependent Neutral Sphingomyelinase

Journal of Vascular Research - Tập 49 Số 4 - Trang 353-362 - 2012
Jacqueline Ohanian1, Simon P. Forman1, Gideon Katzenberg1, Vasken Ohanian1
1Cardiovascular Medicine, University of Manchester, Manchester, UK

Tóm tắt

Endothelin-1 (ET-1) stimulates vascular cell adhesion molecule (VCAM-1) expression, a process associated with arterial remodelling. However, the pathways activated by ET-1 that lead to VCAM-1 expression are not fully understood. It is reported that sphingomyelinases are necessary for VCAM-1 expression in response to cytokines. Our aim was to investigate the role of sphingomyelinases in ET-1-induced VCAM-1 expression. Acid and neutral sphingomyelinase activities were measured in extracts from rat mesenteric small arteries (RMSA). ET-1 (1–100 nmol/l) stimulated neutral but not acid sphingomyelinase. The activation was rapid, peaking within 5 min and transient, returning towards baseline by 10 min and inhibited by BQ-788, GW4869 and SB203580, which are inhibitors of ET<sub>B</sub> receptor, neutral sphingomyelinase and p38MAPK, respectively. Both GW4869 and SB203580 are reported to inhibit activation of neutral sphingomyelinase 2 implicating it in the response to ET-1. Accordingly we investigated the expression of this isoform and found it was present in RMSA, predominantly in endothelial cells. Treatment of RMSA with ET-1 (1–100 nmol/l) for 16 h increased VCAM-1 expression, which was inhibited by GW4869 and SB203580. These results indicate that ET-1 stimulates arterial VCAM-1 expression through p38MAPK-dependent activation of neutral sphingomyelinases. This suggests a role for sphingolipids in ET-1-induced vascular inflammation in cardiovascular disease.

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10.1161%2Fhy09t1.096249

10.1016%2Fj.pharmthera.2005.11.001

10.1161%2F01.CIR.0000144462.08345.B9

10.1097%2FHJH.0b013e3282fc2184

10.1016%2Fj.cardiores.2007.06.004

10.1038%2F332411a0

10.1016%2FS0014-2999%2899%2900042-4

10.1002%2Fart.21572

10.1006%2Fbbrc.1996.1886

10.1093%2Fcvr%2Fcvp026

10.1161%2F01.HYP.0000095980.43859.59

10.1016%2Fj.tcm.2008.11.005

10.1016%2Fj.bbamcr.2007.03.010

10.1210%2Fer.22.2.153

10.1097%2F00004872-200103001-00006

10.1017%2FS1462399411001815

10.1042%2FBJ20100323

10.1161%2FCIRCRESAHA.110.226464

10.1161%2FHYPERTENSIONAHA.110.162719

10.1016%2Fj.bbrc.2009.09.023

10.1016%2FS0014-2999%2800%2900857-8

10.1074%2Fjbc.M609216200

10.1074%2Fjbc.M109.069963

10.1007%2FPL00000836

10.1016%2Fj.ejphar.2008.02.089

10.1093%2Fcvr%2Fcvp030

10.1021%2Fbi061307z

10.1093%2Fcvr%2Fcvn349

10.1124%2Fmol.63.4.886

10.1161%2F01.ATV.0000194074.59584.42

10.1016%2FS0304-3940%2896%2913249-3

10.1161%2Fhq1201.100264

10.1074%2Fjbc.M206747200

10.1016%2F0024-3205%2892%2990331-I

10.1073%2Fpnas.91.11.4892

10.1042%2F0264-6021%3A3510095

10.1161%2FHYPERTENSIONAHA.108.117366

10.1002%2Fhep.21777

10.1016%2FS0895-7061%2801%2902074-X

10.1152%2Fajpheart.00388.2004

10.1159%2F000159151

10.1161%2F01.CIR.0000051459.74466.46

10.1016%2Fj.advenzreg.2010.09.016

10.1016%2Fj.bbrc.2006.04.013

10.1152%2Fajplung.00031.2009

10.1016%2FS0021-9150%2899%2900134-3

10.1038%2Fnrm2329

10.1016%2Fj.yexcr.2011.05.011

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Journal of Vascular Research

Tập 49 Số 4

353-362

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