English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Consequences of postnatal vascular smooth muscle EGFR deletion on acute angiotensin II action

Schreier, B., Huenerberg, M., Rabe, S., Mildenberger, S., Bethmann, D., Heise, C., et al. (2016). Consequences of postnatal vascular smooth muscle EGFR deletion on acute angiotensin II action. CLINICAL SCIENCE, 130(1), 19-33. doi:10.1042/CS20150503.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Schreier, Barbara, Author
Huenerberg, Mirja, Author
Rabe, Sindy, Author
Mildenberger, Sigrid, Author
Bethmann, Daniel, Author
Heise, Christian, Author
Sibilia, Maria, Author
Offermanns, Stefan1, Author           
Gekle, Michael, Author
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

Content

show
hide
Free keywords: GROWTH-FACTOR RECEPTOR; CARDIAC-HYPERTROPHY; CARDIOVASCULAR-SYSTEM; CELLS; TRANSACTIVATION; MICE; HYPERTENSION; ACTIVATION; PATHWAYS; PROMOTESResearch & Experimental Medicine; angiotensin II; endothelin-1; epidermal growth factor receptor; hypotension; mouse model; vascular smooth muscle cells;
 Abstract: Epi dermal growth factor (EGF) receptor (EGFR) is activated by its canonical ligands and transactivated by various vasoactive substances, e.g. angiotensin II (Ang II). Vascular EGFR has been proposed to be involved in vascular tissue homoeostasis and remodelling. Thus, most studies have focused on its role during long-term vascular changes whereas the relevance for acute regulation of vascular function in vivo and ex vivo is insufficiently understood. To investigate the postnatal role of VSMCs (vascular smooth muscle cells) EGFR in vivo and ex vivo, we generated a mouse model with cell-specific and inducible deletion of VSMC EGFR and studied the effect on basal blood pressure, acute pressure response to, among others, Ang II in vivo as well as ex vivo, cardiovascular tissue homoeostasis and vessel morphometry in male mice. In knockout (KO) animals, systolic, diastolic and mean blood pressures were reduced compared with wild-type (WT). Furthermore, Ang II-induced pressure load was lower in KO animals, as was Ang II-induced force development and extracellular-signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in aortic rings from KO animals. By contrast, we observed no difference in force development during application of serotonin, KCl, endothelin-1 or endothelin-1-induced pressure load in KO animals. In addition, nitric oxide (NO)-mediated vasodilation was not affected. Heart weight (HW) increase and up-regulation of aortic and cardiac expression of Ccl2 (chemoattractant protein-2) and serpinE1 (plasminogen activator inhibitor 1) during the transition from 4- to 10-months of age were prevented by VSMC EGFR KO. We conclude that VSMC EGFR is involved in basal blood pressure homoeostasis and acute pressure response to Ang II, and thereby contributes to maturation-related remodelling.

Details

show
hide
Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000369715300003
DOI: 10.1042/CS20150503
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: CLINICAL SCIENCE
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND : PORTLAND PRESS LTD
Pages: - Volume / Issue: 130 (1) Sequence Number: - Start / End Page: 19 - 33 Identifier: ISSN: 0143-5221