TitleDisruption of adipocyte HIF-1 alpha improves atherosclerosis through the inhibition of ceramide generation
AuthorsWang, Pengcheng
Zeng, Guangyi
Yan, Yu
Zhang, Song-yang
Dong, Yongqiang
Zhang, Yangming
Zhang, Xingzhong
Liu, Huiying
Zhang, Zhipeng
Jiang, Changtao
Pang, Yanli
AffiliationPeking Univ, Key Lab Mol Cardiovasc Sci, Minist Educ, Dept Physiol & Pathophysiol,Sch Basic Med Sci, Beijing 100191, Peoples R China
Peking Univ Third Hosp, Ctr Basic Med Res, Inst Med Innovat & Res, Beijing 100191, Peoples R China
Peking Univ Third Hosp, Ctr Reprod Med, Dept Obstet & Gynecol, Beijing 100191, Peoples R China
Peking Univ, Ctr Obes & Metab Dis Res, Sch Basic Med Sci, Beijing 100191, Peoples R China
Peking Univ Third Hosp, Gen Surg Dept, Beijing 100191, Peoples R China
KeywordsADIPOSE-TISSUE
NEUTRAL SPHINGOMYELINASE
INSULIN-RESISTANCE
OBESITY
ACTIVATION
INFLAMMATION
DISEASE
METABOLISM
MECHANISMS
PREVENTS
Issue DateApr-2022
PublisherACTA PHARMACEUTICA SINICA B
AbstractAtherosclerosis is a chronic multifactorial cardiovascular disease. Western diets have been reported to affect atherosclerosis through regulating adipose function. In high cholesterol diet-fed ApoE(-/)(-) mice, adipocyte HIF-1 alpha deficiency or direct inhibition of HIF-1 alpha by the selective pharmacological HIF-1 alpha inhibitor PX-478 alleviates high cholesterol diet-induced atherosclerosis by reducing adipose ceramide generation, which lowers cholesterol levels and reduces inflammatory responses, resulting in improved dyslipidemia and atherogenesis. Smpd3, the gene encoding neutral sphingomyelinase, is identified as a new target gene directly regulated by HIF-1 alpha that is involved in ceramide generation. Injection of lentivirus-SMPD3 in epididymal adipose tissue reverses the decrease in ceramides in adipocytes and eliminates the improvements on atherosclerosis in the adipocyte HIF-la-deficient mice. Therefore, HIF-1 alpha inhibition may constitute a novel approach to slow atherosclerotic progression. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
URIhttp://hdl.handle.net/20.500.11897/646724
ISSN2211-3835
DOI10.1016/j.apsb.2021.10.001
IndexedSCI(E)
Appears in Collections:分子心血管学教育部重点实验室 
第三医院
基础医学院

Files in This Work
There are no files associated with this item.

Web of Science®



Checked on Last Week

Scopus®



Checked on Current Time

百度学术™



Checked on Current Time

Google Scholar™





License: See PKU IR operational policies.