Chronic Over-Expression of Heat Shock Protein 27 Attenuates Atherogenesis and Enhances Plaque Remodeling: A Combined Histological and Mechanical Assessment of Aortic Lesions
Open Access
- 7 February 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (2), e55867
- https://doi.org/10.1371/journal.pone.0055867
Abstract
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 apoE−/− mice (apoE−/−HSP27o/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 apoE−/− mice. After 12 weeks on a high fat diet, serum HSP27 levels rose more than 16-fold in male and female apoE−/−HSP27o/e mice, although females had higher levels than males. Relative to apoE−/− mice, female apoE−/−HSP27o/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 apoE−/−HSP27o/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 apoE−/−HSP27o/e mice (41% in female, 34% in male) compare to apoE−/− counterparts. 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.This publication has 24 references indexed in Scilit:
- Heat Shock Protein 27 Protects Against Atherogenesis via an Estrogen-Dependent MechanismArteriosclerosis, Thrombosis, and Vascular Biology, 2009
- Unfolding the relationship between secreted molecular chaperones and macrophage activation statesCell Stress and Chaperones, 2008
- Extracellular Release of the Atheroprotective Heat Shock Protein 27 Is Mediated by Estrogen and Competitively Inhibits acLDL Binding to Scavenger Receptor-ACirculation Research, 2008
- Genetic Deletion of Pregnancy-Associated Plasma Protein-A Is Associated With Resistance to Atherosclerotic Lesion Development in Apolipoprotein E–Deficient Mice Challenged With a High-Fat DietCirculation Research, 2007
- Extracellular heat shock proteins in cell signalingFEBS Letters, 2007
- Heat shock protein 27 rescues motor neurons following nerve injury and preserves muscle functionExperimental Neurology, 2006
- Comparison of Processing and Sectioning Methodologies for Arteries Containing Metallic StentsJournal of Histochemistry & Cytochemistry, 2006
- Modulation of Estrogen Signaling by the Novel Interaction of Heat Shock Protein 27, a Biomarker for Atherosclerosis, and Estrogen Receptor βArteriosclerosis, Thrombosis, and Vascular Biology, 2005
- Novel Antiinflammatory Vascular Benefits of Systemic and Stent-Based Delivery of EthylisopropylamilorideCirculation, 2004
- The importance of thrombus organization and stellate cell phenotype in collagen I gene expression in human, coronary atherosclerotic and restenotic lesionsCardiovascular Research, 1996