Defective AMPK regulation of cholesterol metabolism accelerates atherosclerosis by promoting HSPC mobilization and myelopoiesis.

ABSTRACT:

Objectives

Dysregulation of cholesterol metabolism in the liver and hematopoietic stem and progenitor cells (HSPCs) promotes atherosclerosis development. Previously, it has been shown that HMG-CoA-Reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway, can be phosphorylated and inactivated by the metabolic stress sensor AMP-activated protein kinase (AMPK). However, the physiological significance of AMPK regulation of HMGCR to atherogenesis has yet to be elucidated. The aim of this study was to determine the role of AMPK/HMGCR axis in the development of atherosclerosis.

Methods

We have generated a novel atherosclerotic-prone mouse model with defects in the AMPK regulation of HMGCR (Apoe^-/-/Hmgcr KI mice). Atherosclerotic lesion size, plaque compositi

SUBMITTER: Lee MKS 

PROVIDER: S-EPMC9124714 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature