SR-BI (Scavenger Receptor BI), Not LDL (Low-Density Lipoprotein) Receptor, Mediates Adrenal Stress Response-Brief Report

被引：11

作者：

Ito, Misa ^{[1
,2
]}

Ye, Xiang ^{[1
]}

Wang, Qian ^{[1
]}

Guo, Ling ^{[1
]}

Hao, Dan ^{[1
,2
]}

Howatt, Deborah ^{[1
]}

Daugherty, Alan ^{[1
,2
,3
]}

Cai, Lei ^{[1
]}

Temel, Ryan ^{[1
,3
]}

Li, Xiang-An ^{[1
,2
,3
]}

机构：

[1] Univ Kentucky, Coll Med, Saha Cardiovasc Res Ctr, BBSRB B255,741 S Limestone, Lexington, KY 40536 USA

[2] Univ Kentucky, Coll Med, Dept Pharmacol & Nutr Sci, Lexington, KY USA

[3] Univ Kentucky, Coll Med, Dept Physiol, Lexington, KY USA

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2020年 / 40卷 / 08期

关键词：

adrenocorticotropic hormone; apolipoproteins B; glucocorticoids; lipoproteins; mice; scavenger receptor type B class I; sepsis; CHOLESTEROL; MICE; HDL; METABOLISM; VARIANT;

D O I：

10.1161/ATVBAHA.120.314506

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: Adrenal gland secretes stress-induced glucocorticoids (iGCs) to coping with stress. Previous study showed that SR-BI (scavenger receptor BI) null (SR-BI-/-) mice failed to generate iGC in stress conditions, suggesting that SR-BI-mediated cholesterol uptake from HDL (high-density lipoprotein) is a key regulator for iGC production. However, the LDL (low-density lipoprotein)/LDLr (LDL receptor) pathway can also provide cholesterol for iGC synthesis, but rodents have limited LDL levels in circulation. Here, we generated SR-BI(-/-)ApoBtg (apolipoprotein B transgenic) mice with normal LDL levels in circulation to determine the relative contribution of the HDL/SR-BI and LDL/LDLr pathways to iGC production in stress conditions. Approach and Results: To obtain mouse models with normal LDL levels, SR-BI(-/-)mice were bred to ApoBtg mice. Then, the F1 SR-BI +/- ApoBtg mice were backcrossed to SR-BI(-/-)to obtain SR-BI(-/-)ApoBtg, SR-BI(-/-)ApoBwt (apolipoprotein B wild type), and SR-BI(+/+)ApoBtg mice. We first examined the lipoprotein profile, which shows a 6.5-fold increase in LDL levels in SR-BI(-/-)ApoBtg mice compared with SR-BI(-/-)ApoBwt mice. Then, we induced stress with adrenocorticotropic hormone and cecal ligation and puncture. One hour after adrenocorticotropic hormone stimulation, SR-BI(+/+)ApoBtg control mice produced iGC (14.9-fold), but both SR-BI(-/-)ApoBwt and SR-BI(-/-)ApoBtg showed no iGC production (P<0.001). Three hours after cecal ligation and puncture treatment, SR-BI(+/+)ApoBtg control mice showed iGC production (6.4-fold), but both SR-BI(-/-)ApoBwt and SR-BI(-/-)ApoBtg mice showed no iGC production (P<0.001). Conclusions: SR-BI(-/-)ApoBtg mice fail to produce iGC in stress conditions even though with restored LDL levels in circulation. These findings clarify that the HDL/SR-BI, not LDL/LDLr, pathway is responsible for iGC production in stress conditions.

引用

页码：1830 / 1837

页数：8

共 26 条

[1] Corticosteroid Therapy Benefits Septic Mice With Adrenal Insufficiency But Harms Septic Mice Without Adrenal Insufficiency [J].