Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression.

Research output: Contribution to journalArticle

Abstract

Vasoconstrictive endothelin type B (ETB) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ETB receptor expression and if extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) signal pathways are involved in this process. Rat mesenteric artery segments were organ cultured in the presence and absence of LDL with or without inhibitors for MAPK kinase 1 and 2 (MEK1/2), p38 and transcription. The upregulation of vasoconstrictive ETB receptor expression was studied using a sensitive myograph, real-time PCR and Western blot. LDL (11, 22 and 44mg protein/L) concentration-dependently induced upregulation of vasoconstrictive ETB receptor expression with increase in the receptor-mediated vasoconstriction, elevated levels of the ETB receptor mRNA and protein expressions, and activation of ERK1/2 and p38 MAPK. Blockage of ERK1/2 and p38 MAPK signal pathways using MEK1/2 inhibitors (PD98059 and U0126) or p38 inhibitors (SB203580 and SB239063) significantly abolished the LDL-induced upregulation of vasoconstrictive ETB receptor expression. Actinomycin D (general transcriptional inhibitor) almost completely inhibited the LDL effects. In conclusion, LDL induces upregulation of vasoconstrictive ETB receptor expression through activation of ERK1/2 and p38 MAPK signal pathway-dependent transcriptional mechanisms.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Other Clinical Medicine
Original languageEnglish
Pages (from-to)42-48
JournalVascular Pharmacology
Volume60
Issue number1
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medicine (Lund) (013230025), Chemical Physics (S) (011001060)

Total downloads

No data available