Regulation of scavenger receptor class BI gene expression by angiotensin II in vascular endothelial cells.
High-density lipoprotein mediates a normal physiological process called reverse cholesterol transport. In this process, a scavenger receptor of the B class (SR-BI)/human homologue of SR-BI, CD36, and LIMPII analogous-1 (hSR-BI/CLA-1) facilitates the cellular uptake of cholesterol from high-density lipoprotein. In endothelial cells, high-density lipoprotein activates endothelial NO synthase via hSR-BI/CLA-1. Angiotensin II (Ang II) is a powerful accelerator of atherosclerosis and modulates the expression of endothelial NO synthase. In the present study, we have examined the role of Ang II on hSR-BI/CLA-1 expression in human umbilical vein endothelial cells. Our results showed that endogenous expression of hSR-BI/CLA-1 was suppressed by exposure to Ang II in human umbilical vein endothelial cells. Administration of the Ang II type-1 receptor blocker olmesartan inhibited Ang II-induced hSR-BI/CLA-1 protein repression. In Ang II-treated cells, high-density lipoprotein had no effect on endothelial NO synthase activation. Ang II decreased transcriptional activity of the hSR-BI/CLA-1 promoter. The inhibitory effect of Ang II on hSR-BI/CLA-1 promoter activity was abrogated by wortmannin and LY294002, specific inhibitors of phosphatidylinositol 3-kinase. Exposure of human umbilical vein endothelial cells to Ang II elicited a rapid phosphorylation of Akt and FoxO1, a known target of Akt signaling. Constitutively active Akt inhibits the activity of the hSR-BI/CLA-1 promoter, and a dominant-negative mutant of Akt or mutagenesis of a FoxO1 response element in the hSR-BI/CLA-1 abolished the ability of Ang II to suppress promoter activity. Together, these results indicate that the phosphatidylinositol 3-kinase/Akt/FoxO1 pathway participates in Ang II suppression of hSR-BI/CLA-1 expression and suggests that the endothelial receptor for hSR-BI/CLA-1 is downregulated by the renin-angiotensin system.
Yu
Xiao
X
Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Murao
Koji
K
Imachi
Hitomi
H
Cao
Wen-Ming
WM
Li
Junhua
J
Matsumoto
Kensuke
K
Nishiuchi
Takamasa
T
Ahmed
Rania A M
RA
Wong
Norman C W
NC
Kosaka
Hiroaki
H
Unterman
Terry G
TG
Ishida
Toshihiko
T
D000730:Androstadienes / Q000494:pharmacology; D000804:Angiotensin II / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D000804:Angiotensin II; D002867:Chromones; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D007093:Imidazoles; D009025:Morpholines; D019001:Nitric Oxide Synthase; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D051122:Scavenger Receptors, Class B; D013777:Tetrazoles; D000077191:Wortmannin; C085126:FOXO1 protein, human; C495124:SCARB1 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C437965:olmesartan