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 Vol. 62; no. 16; pp. 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: Journal Article
• Language: English
• Published: New York, NY Elsevier 15.10.2013
• 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; Human; Rodentia; Cardiovascular disease; Potential; Serum protein; Vascular disease; Vertebrata; Target; Mammalia; Treatment; Mouse; Animal; Cohort study; Atherosclerosis; Clinical biology; Heat shock protein; Observation; Female; Circulatory system; Cardiology; Public health; PBS; atherosclerosis; coronary artery disease; IL; CAD; HFD; major adverse cardiovascular event(s); heat shock protein; IQR; interquartile range; phosphate-buffered saline; heat shock protein 27; coronary disease; MACE; HSP27; high-fat diet; apolipoprotein E; ApoE; interleukin
• 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 (<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. 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.