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.
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 +/- 287 ng/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.
Limor
Rona
R
Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, 6 Weizman St., 64239, Tel Aviv, Israel.
Kaplan
Marielle
M
Sawamura
Tatsuya
T
Sharon
Orli
O
Keidar
Shlomo
S
Weisinger
Gary
G
Knoll
Esther
E
Naidich
Michal
M
Stern
Naftali
N
D000804:Angiotensin II / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D014662:Vasoconstrictor Agents; C099252:oxidized low density lipoprotein; D000804:Angiotensin II; D001092:Arachidonate 12-Lipoxygenase; C458528:ALOX15B protein, human; D001093:Arachidonate 15-Lipoxygenase