Chronic Over-Expression of Heat Shock Protein 27 Attenuates Atherogenesis and Enhances Plaque Remodeling: A Combined Histological and Mechanical Assessment of Aortic Lesions
Author(s)
Type
Journal Article
Abstract
Aims: Expression of Heat Shock Protein-27 (HSP27) is reduced in human coronary atherosclerosis. Over-expression of HSP27
is protective against the early formation of lesions in atherosclerosis-prone apoE2/2 mice (apoE2/2HSP27o/e) - however,
only in females. We now seek to determine if chronic HSP27 over-expression is protective in a model of advanced
atherosclerosis in both male and female apoE2/2 mice.
Methods and Results: After 12 weeks on a high fat diet, serum HSP27 levels rose more than 16-fold in male and female
apoE2/2HSP27o/e mice, although females had higher levels than males. Relative to apoE2/2 mice, female apoE2/2HSP27o/e
mice showed reductions in aortic lesion area of 35% for en face and 30% for cross-sectional sinus tissue sections – with the
same parameters reduced by 21% and 24% in male cohorts; respectively. Aortic plaques from apoE2/2HSP27o/e mice
showed almost 50% reductions in the area occupied by cholesterol clefts and free cholesterol, with fewer macrophages and
reduced apoptosis but greater intimal smooth muscle cell and collagen content. The analysis of the aortic mechanical
properties showed increased vessel stiffness in apoE2/2HSP27o/e mice (41% in female, 34% in male) compare to apoE2/2
counterparts.
Conclusions: Chronic over-expression of HSP27 is atheroprotective in both sexes and coincides with reductions in lesion
cholesterol accumulation as well as favorable plaque remodeling. These data provide new clues as to how HSP27 may
improve not only the composition of atherosclerotic lesions but potentially their stability and resilience to plaque rupture.
is protective against the early formation of lesions in atherosclerosis-prone apoE2/2 mice (apoE2/2HSP27o/e) - however,
only in females. We now seek to determine if chronic HSP27 over-expression is protective in a model of advanced
atherosclerosis in both male and female apoE2/2 mice.
Methods and Results: After 12 weeks on a high fat diet, serum HSP27 levels rose more than 16-fold in male and female
apoE2/2HSP27o/e mice, although females had higher levels than males. Relative to apoE2/2 mice, female apoE2/2HSP27o/e
mice showed reductions in aortic lesion area of 35% for en face and 30% for cross-sectional sinus tissue sections – with the
same parameters reduced by 21% and 24% in male cohorts; respectively. Aortic plaques from apoE2/2HSP27o/e mice
showed almost 50% reductions in the area occupied by cholesterol clefts and free cholesterol, with fewer macrophages and
reduced apoptosis but greater intimal smooth muscle cell and collagen content. The analysis of the aortic mechanical
properties showed increased vessel stiffness in apoE2/2HSP27o/e mice (41% in female, 34% in male) compare to apoE2/2
counterparts.
Conclusions: Chronic over-expression of HSP27 is atheroprotective in both sexes and coincides with reductions in lesion
cholesterol accumulation as well as favorable plaque remodeling. These data provide new clues as to how HSP27 may
improve not only the composition of atherosclerotic lesions but potentially their stability and resilience to plaque rupture.
Date Issued
2013-02-07
Date Acceptance
2013-01-03
Citation
PLOS ONE, 2013, 8 (2)
ISSN
1932-6203
Publisher
PUBLIC LIBRARY SCIENCE
Journal / Book Title
PLOS ONE
Volume
8
Issue
2
Copyright Statement
© 2013 Cuerrier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
ESTROGEN-RECEPTOR-BETA
HEAT-SHOCK-PROTEIN-27
ATHEROSCLEROSIS
APOPTOSIS
ARTERIES
HSP27
Publication Status
Published
Article Number
ARTN e55867