scholarly journals Inhibition of hepatic scavenger receptor-class B type I by RNA interference decreases atherosclerosis in rabbits

2012 ◽  
Vol 222 (2) ◽  
pp. 360-366 ◽  
Author(s):  
Egon Demetz ◽  
Ivan Tancevski ◽  
Kristina Duwensee ◽  
Ursula Stanzl ◽  
Eva Huber ◽  
...  
Keyword(s):  
Rna Interference ◽  
Scavenger Receptor ◽  
Type I ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals HDL modification by secretory phospholipase A2 promotes scavenger receptor class B type I interaction and accelerates HDL catabolism

2000 ◽  
Vol 41 (11) ◽  
pp. 1849-1857 ◽  
Author(s):  
Frederick C. de Beer ◽  
Patrice M. Connell ◽  
J. Yu ◽  
Maria C. de Beer ◽  
Nancy R. Webb ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Scavenger Receptor ◽  
Type I ◽  
Secretory Phospholipase A2 ◽  
Secretory Phospholipase ◽  
Scavenger Receptor Class ◽  
Class B

MS81 LIVER-SPECIFIC LIPOPLEXES FOR THE KNOCKDOWN OF SCAVENGER RECEPTOR CLASS B TYPE I

2010 ◽  
Vol 11 (2) ◽  
pp. 126
Author(s):  
K. Duwensee ◽  
I. Tancevski ◽  
E. Demetz ◽  
P. Eller ◽  
C. Heim ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Type I ◽  
Scavenger Receptor Class ◽  
Class B

scholarly journals Feedback Inhibition of Human Scavenger Receptor Class B Type I Gene Expression by Glucocorticoid in Adrenal and Ovarian Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3214-3224 ◽  
Author(s):  
Sofia Mavridou ◽  
Maria Venihaki ◽  
Olga Rassouli ◽  
Christos Tsatsanis ◽  
Dimitris Kardassis
Keyword(s):  
Gene Expression ◽  
Gene Transcription ◽  
Feedback Inhibition ◽  
Steroid Hormone ◽  
Scavenger Receptor ◽  
Type I ◽  
Mrna Levels ◽  
Ovarian Cells ◽  
Scavenger Receptor Class ◽  
Class B

Scavenger receptor class B type I (SR-BI) facilitates the reverse transport of excess cholesterol from peripheral tissues to the liver via high-density lipoproteins. In steroidogenic tissues, SR-BI supplies cholesterol for steroid hormone production. We show here that the transcription of the human SR-BI gene is subject to feedback inhibition by glucocorticoid in adrenal and ovarian cells. SR-BI mRNA levels were increased in adrenals from corticosterone-insufficient Crh−/− mice, whereas corticosterone replacement by oral administration inhibited SR-BI gene expression in these mice. SR-BI mRNA levels were increased in adrenals from wild-type mice treated with metyrapone, a drug that blocks corticosterone synthesis. Experiments in adrenocortical H295R and ovarian SKOV-3 cells using cycloheximide and siRNA-mediated gene silencing revealed that glucocorticoid-mediated inhibition of SR-BI gene transcription requires de novo protein synthesis and the glucocorticoid receptor (GR). No direct binding of GR to the SR-BI promoter could be demonstrated in vitro and in vivo, suggesting an indirect mechanism of repression of SR-BI gene transcription by GR in adrenal cells. Deletion analysis established that the region of the human SR-BI promoter between nucleotides −201 and −62 is sufficient to mediate repression by glucocorticoid. This region contains putative binding sites for transcriptional repressors that could play a role in SR-BI gene regulation in response to glucocorticoid. In summary, this is the first report showing that glucocorticoid suppress SR-BI expression suggesting that steroidogenic tissues maintain steroid hormone homeostasis by prohibiting SR-BI-mediated high-density lipoprotein cholesterol uptake when the endogenous levels of glucocorticoid are elevated.

Abstract 624: Endothelial Scavenger Receptor Class B, Type I (SR-BI) Mediates LDL Uptake by the Artery Wall and Promotes Atherosclerosis in Hypercholesterolemic Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Linzhang Huang ◽  
Ken Chambliss ◽  
Mohamed Ahmed ◽  
Chieko Mineo ◽  
Philip W Shaul
Keyword(s):  
Endothelial Cells ◽  
Scavenger Receptor ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Type I ◽  
Artery Wall ◽  
Blocking Antibody ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Ldl Uptake

In endothelial cells, high density lipoprotein cholesterol (HDL) binding to scavenger receptor class B, type I (SR-BI) promotes the production of the antiatherogenic signaling molecule nitric oxide (NO) and also endothelial repair. To study how SR-BI in endothelium impacts atherosclerosis, we bred newly-created floxed SR-BI mice, vascular endothelial cadherin promoter-driven Cre recombinase transgenic (VECad-Cre), and apoE -/- mice to generate apoE -/- with normal endothelial SR-BI expression (SR-BI ECIN ;apoE -/- ) or selective deletion of SR-BI from endothelium (SR-BI ECOUT ;apoE -/- ). At weaning all mice were placed on an atherogenic diet (20% fat, 1.25% cholesterol), and plasma lipid profiles and atherosclerosis were evaluated 8 weeks later. Endothelial deletion of SR-BI did not alter the plasma lipid profile. Surprisingly, male SR-BI ECOUT ;apoE -/- mice displayed 63% less atherosclerosis in the en face aorta than male SR-BI ECIN ;apoE -/- mice, aortic root lesions were comparably affected, and similar findings were obtained in females. Recognizing that SR-BI binds both HDL and low density lipoprotein cholesterol (LDL), to then discern how endothelial SR-BI promotes atherosclerosis we determined using Di-I-labeled oxidized LDL (oxLDL) if SR-BI influences oxLDL uptake by endothelial cells. Such uptake is the first step in the endothelial transcytosis that delivers LDL to the artery wall to initiate atherogenesis. OxLDL uptake by primary human aortic endothelial cells was blunted by 87% by SR-BI blocking antibody, and it was also decreased by SR-BI deletion via siRNA, and by the chemical inhibitor of SR-BI BLT-1. Furthermore, SR-BI blocking antibody and BLT-1 caused marked declines in endothelial oxLDL transcytosis. Moreover, 4 hours following IV administration, oxLDL uptake in aorta was decreased by 84% in SR-BI ECOUT ;apoE -/- versus SR-BI ECIN ;apoE -/- mice. These collective findings indicate that endothelial SR-BI plays an important role in atherogenesis, and that it likely does so by mediating LDL uptake into the artery wall. They further suggest that there are mechanisms that govern LDL transport across endothelium that may be targeted to provide novel means to combat atherosclerosis.

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