Serum Heat Shock Protein 27 Levels Represent a Potential Therapeutic Target for Atherosclerosis: Observations From a Human Cohort and Treatment of Female Mice

• Published in: Journal of the American College of Cardiology 2013-10, Vol.62 (16), p.1446-1454
• Main Authors: SEIBERT, Tara A, HIBBERT, Benjamin, HAWKEN, Steven, WILSON, Kumanan R, O'BRIEN, Edward R, CHEN, Yong-Xiang, RAYNER, Katey, SIMARD, Trevor, TIEQIANG HU, CUERRIER, Charles M, XIAOLING ZHAO, DE BELLEROCHE, Jacqueline, CHOW, Benjamin J. W
• Format: Article
• Language: English
• Subjects: Aged; Animals; Atherosclerosis (general aspects, experimental research); Atherosclerosis - blood; Atherosclerosis - diagnosis; Atherosclerosis - drug therapy; Atherosclerosis - physiopathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cohort Studies; Coronary Angiography - methods; Coronary Vessels - pathology; Disease Models, Animal; Female; Heart; HSP27 Heat-Shock Proteins - blood; HSP27 Heat-Shock Proteins - pharmacology; Humans; Male; Medical sciences; Mice; Middle Aged; Multidetector Computed Tomography - methods; Outcome Assessment (Health Care); Plaque, Atherosclerotic - drug therapy; Plaque, Atherosclerotic - pathology; Plaque, Atherosclerotic - physiopathology; Predictive Value of Tests; Prognosis; Treatment Outcome
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2013.05.041

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. 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. 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. 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 (