Page 81 - GTM-1-1

Global Translational Medicine

MINI-REVIEW
A mini-review on quantification of

atherosclerosis in hypercholesterolemic mice

1
1
1
Hui Chen , Deborah A. Howatt , Michael K. Franklin , Naofumi Amioka ,
1
Hisashi Sawada 1,2,3 , Alan Daugherty 1,2,3 *, and Hong S. Lu 1,2,3 *
1 Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States
2 Saha Aortic Center, University of Kentucky, Lexington, Kentucky, United States
3 Department of Physiology, University of Kentucky, Lexington, Kentucky, United States

Abstract

Atherosclerosis is a leading cause of morbidity and mortality in many countries.
Mice are the most frequently used animal model to study the pathogenesis
and molecular mechanisms of atherosclerosis. En face analyses of the aorta and
cross-sections of the aortic root are the two common modes for quantifying
the severity of atherosclerosis in mice. This mini-review introduces these two
methods, discusses their pros and cons, and provides suggestions to optimize the
quantification of atherosclerosis, thereby enhancing rigor and reproducibility in
preclinical research.

Keywords: Atherosclerosis; Aorta; En face; Aortic root; Staining; Mouse

*Corresponding authors:
Hong S. Lu
(hong.lu@uky.edu) 1. Introduction
Alan Daugherty
(alan.daugherty@uky.edu) Atherosclerosis is a chronic complex pathological process. Two classic mouse strains,
Citation: Chen H, Howatt DA, apolipoprotein E-null (ApoE ) mice and low-density lipoprotein receptor-deficient
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Franklin MK, et al., 2022, A (LDLR ) mice, have been widely used to study the pathogenesis and molecular
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mini-review on quantification
of atherosclerosis in mechanisms of atherosclerosis [1-3] . Recently, mice manipulated with a proprotein
hypercholesterolemic mice. Global convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutation have become
Transl Med, 1(1): 76.
https://doi.org/10.36922/gtm.v1i1.76 a popular model to study atherosclerosis. Briefly, normocholesterolemic mice are
injected with adeno-associated viruses (AAVs) containing either the human D374Y
Received: April 24, 2022 [4-8]
Accepted: June 2, 2022 or mouse D377Y gain-of-function mutation of PCSK9 . This manipulation leads
Published Online: June 14, 2022 to LDLR degradation, thereby mimicking the LDLR mouse model. The benefits
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Copyright: © 2022 Author(s). of using AAVs expressing gain-of-function PCSK9 mutants are two-fold: First, it
This is an Open Access article saves both time and expense for mouse breeding; second, in contrast to constitutive
distributed under the terms of the deletion of LDLR in LDLR mice, this approach can be performed to delete LDLR in
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Creative Commons Attribution
[9]
License, permitting distribution, adult mice .
and reproduction in any medium,
provided the original work is In these hypercholesterolemic mouse models, the atherosclerosis-prone locations are
properly cited. the aorta and the major branches of the aortic arch. Quantification of lesion areas in
Publisher’s Note: AccScience selected vascular beds has been considered a “gold standard” for evaluating the severity
Publishing remains neutral with of atherosclerosis. This brief review introduces and discusses the two commonly used
regard to jurisdictional claims in
published maps and institutional methods, en face analysis in the aortic surface and cross-sections of the aortic root, to
affiliations. quantify atherosclerotic lesion size in mice.

Volume 1 Issue 1 (2022) 1 https://doi.org/10.36922/gtm.v1i1.76