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Cellular and Molecular Biology Letters

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1689-1392
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Volume 20, Issue 5

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Ramipril inhibits high glucose-stimulated up-regulation of adhesion molecules via the ERK1/2 MAPK signaling pathway in human umbilical vein endothelial cells

Moo Hyun Kim / Hae Min Kang
  • Department of Ophthalmology, International St. Mary’s Hospital, College of Medicine, Catholic Kwandong University, Incheon, Korea
  • Other articles by this author:
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/ Chae-Eun Kim / Seongho Han / Sung-Whan Kim
Published Online: 2016-03-05 | DOI: https://doi.org/10.1515/cmble-2015-0053

Abstract

Ramipril has recently been shown to have anti-atherogenic properties. However, the specific mechanisms underlying these effects remain unclear. The purpose of this study was to determine the effects of ramipril on induction of adhesion molecules in human umbilical vein endothelial cells (HUVECs) using high-glucose (HG) conditions and to investigate possible underlying molecular mechanisms. The effects of ramipril on expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 production, and ERK phosphorylation were examined in HG-induced HUVECs with inhibitors targeting the mitogen-activated protein kinase (MAPK) signaling pathway. HG induced the expression of the adhesion molecules ICAM-1 and VCAM-1. Pretreatment with ramipril drastically inhibited ICAM-1 and VCAM-1 production in a time- and dose-dependent manner. Moreover, upon investigating the effects of ramipril on the MAPK/extracellular signal-regulated kinase (ERK) signaling pathway, we found that ramipril completely inhibited HG-induced phosphorylation of ERK1/2. ERK inhibitors completely prevented the inhibitory effect of HG. This study demonstrated that ramipril reduces HG-stimulated induction of ICAM-1 and VCAM-1 expression via MAPK signaling, which may be useful for inhibition of atherosclerosis.

Keywords: ACE inhibitor; Adhesion; Atherosclerosis; Cardiovascular risk; Endothelial cells; ERK pathway; Glucose; Inhibitor; MAPK; Ramipril

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About the article

Received: 2015-09-03

Accepted: 2015-11-12

Published Online: 2016-03-05

Published in Print: 2015-12-01


Citation Information: Cellular and Molecular Biology Letters, Volume 20, Issue 5, Pages 937–947, ISSN (Online) 1689-1392, DOI: https://doi.org/10.1515/cmble-2015-0053.

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