Published online before print July 12, 2004, doi: 10.1161/01.CIR.0000136814.87170.B1
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(Circulation. 2004;110:2216-2219.)
© 2004 American Heart Association, Inc.
Vascular Medicine |
Identification by a Differential Proteomic Approach of Heat Shock Protein 27 as a Potential Marker of Atherosclerosis
From the Vascular Research Laboratory (J.L.M.-V., L.M.B.-C., S.H.-M., J.E.), Department of Immunology (M.C.D., F.V.), and Department of Cardiology Fundación Jiménez Díaz (J.T.), Autónoma University, Madrid, Spain; U460 INSERM, Cardiovascular Remodeling, CHU X-Bichat, Paris, France (O.M., A.L., J.-B.M); the Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark (O.N.J.); and the Proteomic Unit, Complutense University, Madrid, Spain (F.V.).
Correspondence to Professor Jesús Egido, MD, Vascular Research Laboratory, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040, Madrid, Spain. E-mail jegido{at}fjd.es
Received December 17, 2003; de novo received April 22, 2004; revision received May 26, 2004; accepted May 28, 2004.
Background— We hypothesized that normal and pathological vessel walls display a differential pattern of secreted proteins. We have recently set up the conditions for comparing secretomes from carotid atherosclerotic plaques and control arteries using a proteomic approach to assess whether differentially secreted proteins could represent markers for atherosclerosis.
Methods and Results— Normal endartery segments and different regions of endarterectomy pieces (noncomplicated/complicated plaques) were incubated in protein-free medium, and the released proteins were analyzed by 2D electrophoresis (2-DE). Among the differently secreted proteins, we have identified heat shock protein-27 (HSP27). Surprisingly, compared with control arteries, HSP27 release was drastically decreased in atherosclerotic plaques and barely detectable in complicated plaque supernatants. HSP27 was expressed primarily by intact vascular cells of normal arteries and carotid plaques (immunohistochemistry). Plasma detection of soluble HSP27 showed that circulating HSP27 levels are significantly decreased in the blood of patients with carotid stenosis relative to healthy subjects (0.19 [0.1 to 1.95] versus 83 [71.8 to 87.8]) ng/mL, P<0.0001).
Conclusions— HSP27 secretion is decreased in complicated atherosclerotic plaques, and sHSP27 plasma levels are decreased in atherosclerotic patients compared with healthy subjects. Plasma sHSP27 levels could be a potential index of atherosclerosis, although further validation is needed in large patient cohorts.
Key Words: plasma • cells • muscle, smooth • electrophoresis
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