Angiotensin II increases the expression of lectin-like oxidized low-density lipoprotein receptor-1 in human vascular smooth muscle cells via a lipoxygenase-dependent pathway

Rona Limor, Marielle Kaplan, Tatsuya Sawamura, Orli Sharon, Shlomo Keidar, Gary Weisinger, Esther Knoll, Michal Naidich, Naftali Stern

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a membrane protein that can act as a surface endocytosis receptor for oxidized LDL (ox-LDL). As increased cellular uptake of ox-LDL by macrophages and activated smooth muscle cells may transform these cells into foam cells, potential interactions among LDL oxidation, ox-LDL uptake, and regulators of vascular smooth muscle cell function are of obvious interest. The objective of this study was to examine the effect of angiotensin II (AII) on the expression of LOX-1 and ox-LDL degradation in human vascular smooth muscle cells (VSMC). Methods: We performed in vitro experiments in a human VSMC line (T/G HA-VSMC) derived from normal aortic VSMC, using standards methods. Results: We found that AII (10-7mol/L) increased the expression of LOX-1 (∼2.5-fold, P <. 0001) in association with higher degradation of ox-LDL by HA-SMC (from 4019 ± 529 ng/mg cell protein to 6207 ± 287ng/mg cell protein; P =. 0033). AII also increased the expression of 12-lipoxygenase (12-LO) and 15-lipoxygenase (15-LO) by ∼2.2-fold (P =. 03) and ∼3-fold (P =. 006), respectively. In addition, AII (10-7mol/L) increased the release of 12- and 15-hydroxyeicosatetraenoic acid from VSMC within 10 min ∼3-fold (P =. 03) and 50% (P <. 05), respectively. Conclusions: Our study findings provide evidence that angiotensin II upregulates LOX-1 and 12-LO and 15-LO expression in human VSMC, thereby potentially providing mechanisms for both accelerated LDL oxidation within the cell and the internalization of exogenous ox-LDL, two processes that could increase the susceptibility of human VSMC to further transformation into foam cells.

Original languageEnglish
Pages (from-to)299-307
Number of pages9
JournalAmerican Journal of Hypertension
Volume18
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Keywords

  • 12-LO
  • 15-LO
  • Human smooth muscle cells
  • LOX-1

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