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 andResults-Normal endartery segments and different regions of endarterectomy pieces (noncomplicated/ complicated plaques) were incubated in protein-free medium, and the released proteinswere 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. Background-We hypothesized that normal and pathological vessel walls display differential patterns 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 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 wasaalysis by intact vascular cells of normal arteries and carotid plaques (immunohistochemistry). Plasma detection of soluble HSP27 were 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 further validation is needed in large patient cohorts.