Endogenous expression of C-reactive protein is increased in active (ulcerated noncomplicated) human carotid artery plaques.
OBJECTIVE
There is growing evidence suggesting that C-reactive protein (CRP) is an effecter molecule able to induce and promote atherothrombosis. The presence of CRP in atherosclerotic plaques may reflect local production or infiltration from circulating CRP increased in general inflammatory responses. Our aim was to analyze the presence of CRP in human advanced carotid artery plaques with differential anatomo-pathological characteristics and to assess local expression of CRP and other proinflammatory genes in these lesions.


METHODS
Human carotid artery specimens from 38 patients undergoing scheduled endarterectomy were classified into 3 groups: ulcerated (noncomplicated) (UNC, n=19), fibrous (F, n=12) and ulcerated (complicated/hemorrhagic) plaques (UC, n=7). The presence of CRP was evaluated by immunohistochemistry, and plasma samples were screened for circulating high-sensitivity C-reactive protein. TaqMan Low-density Arrays were used for study of genes related to inflammation (CRP, interleukin-6, macrophage colony-stimulating factor-1, monocyte chemotactic protein-1, cyclooxygenase-2).


RESULTS
CRP mRNA levels were predominantly detected in UNC-high risk plaques but not in UC (P=0.001). UNC also exhibit the highest expression levels of other genes involved in the inflammatory responses: cyclooxygenase-2 (P<0.005 versus F and versus UC), IL-6 (P<0.005 versus F and versus UC) and monocyte chemoattractant protein-1 (P<0.01 versus F and versus UC). Plaque CRP mRNA levels correlated with immunohistochemical findings but were independent of plasma high-sensitivity CRP. In UNC plaques endothelial cells and inflammatory cells were strongly positive for CRP around areas of newly formed microvessels.


CONCLUSIONS
In human high-risk carotid artery plaques (UNC) CRP expression reflects an active proinflammatory stage. Local synthesis of CRP could be involved in plaque neovascularization and increased risk of hemorrhagic transformation.
Krupinski
Jerzy
J
Department of Neurology, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain. krupinski@csub.scs.es
Turu
Marta Miguel
MM
Martinez-Gonzalez
Jose
J
Carvajal
Ana
A
Juan-Babot
Josep Oriol
JO
Iborra
Elena
E
Slevin
Mark
M
Rubio
Francisco
F
Badimon
Lina
L
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002097:C-Reactive Protein / Q000096:biosynthesis*; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D018932:Chemokine CCL2; D015850:Interleukin-6; D016173:Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein; D051546:Cyclooxygenase 2