HSP70 induces liver X receptor pathway activation and cholesterol reduction in vitro and in vivo.

ABSTRACT:

Objective

Heat Shock Proteins (HSPs) maintain cellular homeostasis under stress. HSP70 represents a major stress-inducible family member and has been identified as a druggable target in inherited cholesterol-sphingolipid storage diseases. We investigated if HSP70 modulates cholesterol accumulation in more common conditions related to atherogenesis.

Methods

We studied the effects of recombinant HSP70 in cholesterol-laden primary macrophages from human blood donors and pharmacological HSP70 upregulation in high-cholesterol diet fed zebrafish.

Results

Recombinant HSP70 facilitated cholesterol removal from primary human macrophage foam cells. RNA sequencing revealed that HSP70 induced a robust transcriptional re-programming, including upregulation of key targets of liver

SUBMITTER: Gungor B 

PROVIDER: S-EPMC6822257 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature