Published Online
on April 6, 2006

A more recent version of this article appeared on May 1, 2006

This Article Full Text (PDF) All Versions of this Article: 37/5/1200    most recent 01.STR.0000217386.37107.bev1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krupinski, J. Articles by Badimon, L. Search for Related Content PubMed PubMed Citation Articles by Krupinski, J. Articles by Badimon, L. Pubmed/NCBI databases Substance via MeSH Related Collections Angiogenesis Pathophysiology Gene expression Carotid Stenosis

Submitted on December 13, 2005
Revised on January 18, 2006
Accepted on February 2, 2006

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; and 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.

^* To whom correspondence should be addressed. 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

This article has been cited by other articles:

				B. Molins, E. Pena, G. Vilahur, C. Mendieta, M. Slevin, and L. Badimon C-Reactive Protein Isoforms Differ in Their Effects on Thrombus Growth Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2239 - 2246. [Abstract] [Full Text] [PDF]

				F. Montecucco, S. Steffens, F. Burger, G. Pelli, C. Monaco, and F. Mach C-reactive protein (CRP) induces chemokine secretion via CD11b/ICAM-1 interaction in human adherent monocytes J. Leukoc. Biol., October 1, 2008; 84(4): 1109 - 1119. [Abstract] [Full Text] [PDF]

				D. Xing, F. G. Hage, Y.-F. Chen, M. A. McCrory, W. Feng, G. A. Skibinski, E. Majid-Hassan, S. Oparil, and A. J. Szalai Exaggerated Neointima Formation in Human C-Reactive Protein Transgenic Mice Is IgG Fc Receptor Type I (Fc{gamma}RI)-Dependent Am. J. Pathol., January 1, 2008; 172(1): 22 - 30. [Abstract] [Full Text] [PDF]

				M. Boehme, F. Kaehne, A. Kuehne, W. Bernhardt, M. Schroder, W. Pommer, C. Fischer, H. Becker, C. Muller, and R. Schindler Pentraxin 3 is elevated in haemodialysis patients and is associated with cardiovascular disease Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2224 - 2229. [Abstract] [Full Text] [PDF]

				P. Gao, Z.-q. Chen, Y.-h. Bao, L.-q. Jiao, and F. Ling Correlation Between Carotid Intraplaque Hemorrhage and Clinical Symptoms: Systematic Review of Observational Studies Stroke, August 1, 2007; 38(8): 2382 - 2390. [Abstract] [Full Text] [PDF]