Serum heat shock protein 27 levels represent a potential therapeutic target for atherosclerosis: observations from a human cohort and treatment of female mice.

Abstract

OBJECTIVES:

The aim of this study was to evaluate the potential of serum heat shock protein 27 (HSP27) as a therapeutic target in coronary artery disease.

BACKGROUND:

Expression of HSP27 in human coronary arteries diminishes with the progression of atherosclerosis, whereas ubiquitous HSP27 overexpression in apolipoprotein E(-/-) (ApoE(-/-)) mice attenuates atherogenesis. However, it remains unclear whether increasing serum HSP27 levels alone is sufficient for atheroprotection.

METHODS:

Low- and intermediate-risk patients undergoing coronary or computed tomography angiography had serum HSP27 levels measured. Elevated serum HSP27 levels in female atheroprone ApoE(-/-) mice were achieved by transplantation with HSP27 overexpressing bone marrow or by administering recombinant HSP27.

RESULTS:

Patients with >50% stenosis in any major epicardial artery had lower HSP27 levels compared with those free of atherosclerosis (median [interquartile range]: 2,176 pg/ml [551-5,475] vs. 6,200 pg/ml [2,575-9,560]; p < 0.001). After a 5-year period of clinical follow-up, low serum HSP27 levels (<50th percentile) were predictive of subsequent major adverse cardiovascular events (hazard ratio: 2.93, 95% confidence interval: 1.06 to 8.12; p = 0.04). In experimental murine models of atherosclerosis, increasing serum HSP27 levels both reduced de novo atherosclerotic lesion formation and enhanced features of plaque stability.

CONCLUSIONS:

In humans, low serum HSP27 levels are associated with the presence of coronary artery disease and prognostic of future adverse clinical events. In mouse models of atherosclerosis, increasing HSP27 levels reduced lesion progression and promoted features of plaque stability. Serum HSP27 levels may represent a potential therapeutic target for atherosclerosis.

• Authors: Tara A Seibert, Benjamin Hibbert, Yong-Xiang Chen, Katey Rayner, Trevor Simard, Tieqiang Hu, Charles M Cuerrier, Xiaoling Zhao, Jacqueline de Belleroche, Benjamin J W Chow, Steven Hawken, Kumanan R Wilson, Edward R O'Brien
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 62 Issue 16 Pg. 1446-54 (Oct 15 2013) ISSN: 1558-3597 [Electronic] United States
• PMID: 23764828 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• HSP27 Heat-Shock Proteins

Topics

• Aged
• Animals
• Atherosclerosis (blood, diagnosis, drug therapy, physiopathology)
• Cohort Studies
• Coronary Angiography (methods)
• Coronary Vessels (pathology)
• Disease Models, Animal
• Female
• HSP27 Heat-Shock Proteins (blood, pharmacology)
• Humans
• Male
• Mice
• Middle Aged
• Multidetector Computed Tomography (methods)
• Outcome Assessment, Health Care
• Plaque, Atherosclerotic (drug therapy, pathology, physiopathology)
• Predictive Value of Tests
• Prognosis
• Treatment Outcome