Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Maria Gomez

Maria Gomez

Professor

Maria Gomez

Cholesterol depletion impairs vascular reactivity to endothelin-1 by reducing store-operated Ca2+ entry dependent on TRPC1.

Author

  • Andreas Bergdahl
  • Maria Gomez
  • Karl Dreja
  • Shang-Zhong Xu
  • Mikael Adner
  • David J Beech
  • Jonas Broman
  • Per Hellstrand
  • Karl Swärd

Summary, in English

The reactivity of the vascular wall to endothelin-1 (ET-1) is influenced by cholesterol, which is of possible importance for the progression of atherosclerosis. To elucidate signaling steps affected, the cholesterol acceptor methyl-ß-cyclodextrin (mßcd, 10 mmol/L) was used to manipulate membrane cholesterol and disrupt caveolae in intact rat arteries. In endothelium-denuded caudal artery, contractile responsiveness to 10 nmol/L ET-1 (mediated by the ETA receptor) was reduced by mßcd and increased by cholesterol. Neither ligand binding nor colocalization of ETA and caveolin-1 was affected by mßcd. Ca2+ inflow via store-operated channels after depletion of intracellular Ca2+ stores was reduced in mßcd-treated caudal arteries, as shown by Mn2+ quench rate and intracellular [Ca2+] response. Expression of TRPC1, 3, and 6 was detected by reverse transcriptase–polymerase chain reaction, and colocalization of TRPC1 with caveolin-1 was reduced by mßcd, as seen by immunofluorescence. Part of the contractile response to ET-1 was inhibited by Ni2+ (0.5 mmol/L) and by a TRPC1 blocking antibody. In the basilar artery, exhibiting less store-operated channel activity than the caudal artery, ET-1–induced contractions were insensitive to the TRPC1 blocking antibody and to mßcd. Increased store-operated channel activity in basilar arteries after organ culture correlated with increased sensitivity of ET-1 contraction to mßcd. These results suggest that cholesterol influences vascular reactivity to ET-1 by affecting the caveolar localization of TRPC1.

Department/s

  • Vascular Physiology
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Department of Clinical Sciences, Malmö
  • Clinical and Experimental Allergy Research
  • Neurophysiology

Publishing year

2003

Language

English

Pages

839-847

Publication/Series

Circulation Research

Volume

93

Issue

9

Document type

Journal article

Publisher

American Heart Association

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • methyl-ß-cyclodextrin
  • arterial smooth muscle
  • endothelin
  • caveolae
  • store-operated Ca2+ channels

Status

Published

Research group

  • Vascular Physiology
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Clinical and Experimental Allergy Research
  • Neurophysiology

ISBN/ISSN/Other

  • ISSN: 0009-7330