Atorvastatin modulates the profile of proteins released by human atherosclerotic plaques.
The mechanisms by which hydroxymethylglutaryl CoenzymeA reductase inhibitors (statins) reduce atherosclerotic cardiovascular morbidity and mortality remain poorly understood. Statins have been shown to modulate the levels of different inflammatory proteins both in carotid atherosclerotic plaques and in the blood of patients with atherosclerosis. In this work, we hypothesize that statins could also modulate the levels of the proteins secreted by cultured atherosclerotic plaques. Thus, the secretomes obtained from complicated atherosclerotic plaques incubated in the presence/absence of atorvastatin (10 micromol/l, 24 h) were analysed and compared by two-dimensional electrophoresis, considering the fibrous adjacent areas as controls. In total, 54 proteins (83 protein isoforms) were identified by Mass Spectrometry (MS): 24 proteins were increased and 20 proteins decreased in atheroma plaque supernatants compared to controls. Some of these proteins, like Cathepsin D, could play a significant role in plaque instability, becoming a potential target for therapeutical treatment. Interestingly, 66% of the proteins differentially released by atherosclerotic plaques reverted to control values after administration of atorvastatin, among them, Cathepsin D. Moreover, plaques obtained from patients who received atorvastatin treatment prior to carotid endarterectomy showed decreased Cathepsin D expression relative to plaques from non-treated patients. In conclusion, this proteomic approach has shown that statins are able to modulate the secretome of atherosclerotic plaques, and new therapeutical targets for statins have been characterised.
Durán
M Carmen
MC
Department of Immunology, Fundación Jiménez Díaz, Autónoma University, Madrid, Spain.
Martín-Ventura
Jose L
JL
Mohammed
Shabaz
S
Barderas
María G
MG
Blanco-Colio
Luis M
LM
Mas
Sebastián
S
Moral
Verónica
V
Ortega
Luis
L
Tuñón
Jose
J
Jensen
Ole N
ON
Vivanco
Fernando
F
Egido
Jesús
J
D000069059:Atorvastatin; D015153:Blotting, Western; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D002402:Cathepsin D / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism; D016000:Cluster Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D011506:Proteins / Q000032:analysis* / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011506:Proteins; D011758:Pyrroles; D000069059:Atorvastatin; D002402:Cathepsin D