Heat shock protein 70 accelerates atherosclerosis by downregulating the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway.

Biochim Biophys Acta Mol Cell Biol Lipids

Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Medical Research Experiment Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China. Electronic address:

Published: August 2018

Background And Aims: Recent studies have suggested that heat shock protein 70 (HSP70) may play critical roles in cardiovascular disease. However, the effects of HSP70 on the development of atherosclerosis in apoE mice remain largely unknown. This study was to investigate the role and potential mechanism of HSP70 in atherosclerosis.

Methods: HSP70 was overexpressed in apoE mice and THP-1-derived macrophages with lentiviral vectors. Oil Red O, hematoxylin-eosin, and Masson staining were performed to evaluate atherosclerotic plaque in apoE mice fed the Western type diet. Moreover, immunostaining was employed to detect the expression of relative proteins in aortic sinus. Reporter gene and chromatin immunoprecipitation were performed to analyze the effect of Elk-1 on the promoter activity of ABCA1 and ABCG1; [H] labeled cholesterol was used to assess the capacity of cholesterol efflux and reverse cholesterol transport (RCT).

Results: Our results showed that HSP70 increased lipid accumulation in arteries and promoted the formation of atherosclerotic lesion. The capacity of cholesterol efflux was reduced in peritoneal macrophages isolated from HSP70-overexpressed apoE mice. The levels of ABCA1 and ABCG1 expression were also reduced in the peritoneal macrophages and the aorta from apoE mice in response to HSP70. The c-Jun N-terminal kinase (JNK) and ETS transcription factor (Elk-1) played a critical role in HSP70-induced downregulation ABCA1 and ABCG1. Further, HSP70 reduced RCT from macrophages to plasma, liver, and feces in apoE mice.

Conclusions: HSP70 promotes the progression of atherosclerosis in apoE mice by suppressing the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway.

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http://dx.doi.org/10.1016/j.bbalip.2018.04.011DOI Listing

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