| Am J Hypertens. 2005 Mar;18(3):299-307 |
|
| 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 |
|
| Limor R, Kaplan M, Sawamura T, Sharon O, Keidar S, Weisinger G, Knoll
E, Naidich M, Stern N. |
|
| Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv
Sourasky Medical Center, Tel Aviv, Israel |
|
| 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(-7)mol/L) increased the expression of
LOX-1 ( approximately 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 approximately 2.2-fold (P = .03) and approximately 3-fold
(P = .006), respectively. In addition, AII (10(-7)mol/L) increased
the release of 12- and 15-hydroxyeicosatetraenoic acid from VSMC within
10 min approximately 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. |
