Journal article
Defective AMPK regulation of cholesterol metabolism accelerates atherosclerosis by promoting HSPC mobilization and myelopoiesis
MKS Lee, OD Cooney, X Lin, S Nadarajah, D Dragoljevic, K Huynh, DA Onda, S Galic, PJ Meikle, T Edlund, MD Fullerton, BE Kemp, AJ Murphy, K Loh
Molecular Metabolism | ELSEVIER | Published : 2022
Open access
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 ..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
National Health and Medical Research Council of Australia; project grant #1156634 (KL) National Health and Medical Research Council of Australia; project grant #1085460 (BEK) National Health and Medical Research Council of Australia; fellowship#1078752 (BEK) National Health and Medical Research Council of Australia; fellowship#1085752 (AJM) National Health and Medical Research Council of Australia; project grant #1106154 (AJM) National Health and Medical Research Council of Australia; project grant #1142938 (AJM) National Heart Foundation; future leader fellowship #100440 (AJM) L.E.W Carty Charitable Fund (KL). CSL Centenary Award (AJM) Victorian Governments Operational Infrastructure Support Program.