Identification by a differential proteomic approach of heat shock protein 27 as a potential marker of atherosclerosis.
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.


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.
Martin-Ventura
Jose Luis
JL
Vascular Research Laboratory, Autónoma University, Madrid, Spain.
Duran
Mari Carmen
MC
Blanco-Colio
Luis Miguel
LM
Meilhac
Olivier
O
Leclercq
Anne
A
Michel
Jean-Baptiste
JB
Jensen
Ole N
ON
Hernandez-Merida
Sergio
S
Tuñón
José
J
Vivanco
Fernando
F
Egido
Jesús
J
D000368:Aged; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000097:blood / Q000503:physiopathology* / Q000601:surgery; D002846:Chromatography, Affinity; D017077:Culture Media, Conditioned / Q000737:chemistry; D016894:Endarterectomy, Carotid; D005260:Female; D005263:Femoral Artery / Q000378:metabolism / Q000473:pathology; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D009924:Organ Culture Techniques; D010766:Phosphorylation; D020033:Protein Isoforms / Q000032:analysis; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D017077:Culture Media, Conditioned; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D020033:Protein Isoforms