Published Online
on July 12, 2004

A more recent version of this article appeared on October 12, 2004

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Submitted on December 17, 2003
Revised on May 26, 2004
Accepted on May 28, 2004

Identification by a Differential Proteomic Approach of Heat Shock Protein 27 as a Potential Marker of Atherosclerosis

Jose Luis Martin-Ventura PhD, Mari Carmen Duran BSc, Luis Miguel Blanco-Colio PhD, Olivier Meilhac PhD, Anne Leclercq BSc, Jean-Baptiste Michel MD, PhD, Ole N. Jensen PhD, Sergio Hernandez-Merida BSc, José Tuñón MD, PhD, Fernando Vivanco PhD, and Jesús Egido MD, PhD^*

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.).

^* To whom correspondence should be addressed. E-mail: jegido{at}fjd.es.

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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