%0 Journal Article
%T Disruption of adipocyte HIF-1α improves atherosclerosis through the inhibition of ceramide generation.
%A Wang P
%A Zeng G
%A Yan Y
%A Zhang SY
%A Dong Y
%A Zhang Y
%A Zhang X
%A Liu H
%A Zhang Z
%A Jiang C
%A Pang Y
%A Wang P
%A Zeng G
%A Yan Y
%A Zhang SY
%A Dong Y
%A Zhang Y
%A Zhang X
%A Liu H
%A Zhang Z
%A Jiang C
%A Pang Y
%J Acta Pharm Sin B
%V 12
%N 4
%D Apr 2022
%M 35847503
%F 14.903
%R 10.1016/j.apsb.2021.10.001
%X Atherosclerosis 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-1α deficiency or direct inhibition of HIF-1α by the selective pharmacological HIF-1α 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-1α 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-1α-deficient mice. Therefore, HIF-1α inhibition may constitute a novel approach to slow atherosclerotic progression.