Hypercholesterolemia Causes Circadian Dysfunction: A Potential Risk Factor for Cardiovascular Disease

EBioMedicine
Makoto AkashiKoichi Node

Abstract

Hypercholesterolemia is a well-known risk factor for a wide range of diseases in developed countries. Here, we report that mice lacking functional LDLR (low density lipoprotein receptor), an animal model of human familial hypercholesterolemia, show circadian abnormalities. In free running behavioral experiments in constant darkness, these mice showed a prolonged active phase and distinctly bimodal rhythms. Even when the circadian rhythms were entrained by light and dark cycles, these mice showed a significant attenuation of behavioral onset intensity at the start of the dark period. Further, we hypothesized that the combination of hypercholesterolemia and circadian abnormalities may affect cardiovascular disease progression. To examine this possibility, we generated LDLR-deficient mice with impaired circadian rhythms by simultaneously introducing a mutation into Period2, a core clock gene, and found that these mice showed a significant enlargement of artery plaque area with an increase in inflammatory cytokine IL-6 levels. These results suggest that circadian dysfunction may be associated with the development or progression of cardiovascular diseases.

Citations

Jan 7, 2021·PLoS Computational Biology·Michael C Tackenberg, Jacob J Hughey
Jan 11, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yu-Sheng LinChao-Yung Wang
Feb 23, 2021·Journal of Cellular Physiology·Xinpeng ChenJunying Miao
Jun 13, 2021·Autoimmunity Reviews·Kun XiangDe-Guang Wang
Jul 9, 2021·Circulation·Andreas SchoberMaliheh Nazari-Jahantigh
Nov 21, 2020·Nutrition Research·Ana Beatriz Rezende PaulaMauro César Isoldi

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Methods Mentioned

BETA
PCR

Software Mentioned

ImageJ
Clock Lab

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