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(Stroke. 2006;37:1200.)
© 2006 American Heart Association, Inc.

Original Contributions

Endogenous Expression of C-Reactive Protein Is Increased in Active (Ulcerated Noncomplicated) Human Carotid Artery Plaques

Jerzy Krupinski, MD, PhD; Marta Miguel Turu, Msc; Jose Martinez-Gonzalez, PhD; Ana Carvajal, Msc; Josep Oriol Juan-Babot; Elena Iborra, MD; Mark Slevin, PhD; Francisco Rubio, MD Lina Badimon, PhD

From the Department of Neurology (J.K., M.M.T., A.C., F.R.), Stroke Unit, University Hospital of Bellvitge (HUB), and IDIBELL, Barcelona, Spain; Cardiovascular Research Centre (J.K., M.M.T, J.M.-G., J.O.J.-B., L.B.), IIBB/CSIC-HSCSP-UAB, Barcelona, Spain; the Department of Vascular Surgery (E.I.), University Hospital of Bellvitge (HUB), Barcelona, Spain; and the Department of Biological Sciences (M.S.), John Dalton Building, Manchester Metropolitan University, Manchester, UK.

Correspondence to Jerzy Krupinski, MD, PhD, Department of Neurology, Stroke Unit, Hospital Universitari de Bellvitge, Feixa Llarga s/n 08907 L’Hospitalet de Llobregat, Barcelona, Spain. E-mail krupinski{at}csub.scs.es

Background and Purpose— 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.

Key Words: angiogenesis • carotid atherosclerosis • C-reactive protein

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