on April 5, 2007
Published online before print April 5, 2007, doi: 10.1161/ATVBAHA.107.140913
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Submitted on August 17, 2006
Accepted on March 15, 2007
Low Levels of Nogo-B in Human Carotid Atherosclerotic Plaques Are Associated With an Atheromatous Phenotype, Restenosis, and Stenosis Severity
Juan A. Rodriguez-Feo ;
From the Department of Cardiology, Experimental Cardiology Laboratory (J.A.R.-F., W.E.H., B.A.N.V., D.P.V.d.K., G.P.), University Medical Center, Utrecht, the Netherlands; the Interuniversity Cardiology Institute of the Netherlands (ICIN) (D.P.V.d.K., G.P.), Utrecht, the Netherlands; the Department of Vascular Surgery (W.E.H., B.A.N.V., F.L.M.), University Medical Center, Utrecht, the Netherlands; the Department of Pharmacology (J.P., Y.G., W.C.S.), Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Conn; the Julius Center for Health Sciences and Primary Care (Y.v.d.G.), Utrecht, The Netherlands; and the Department of Surgery (G.T.), Yale University School of Medicine, New Haven, Conn.
* To whom correspondence should be addressed. E-mail: g.pasterk{at}umcutrecht.nl.
Objective--Reticulon-4/Nogo (Nogo-B) protects mouse arteries from lumen loss by reducing smooth muscle cell (SMC) migration and intimal thickening. Our goal was to determine plaque and circulating levels of Nogo-B in atherosclerotic and control subjects. Therefore, we studied the relationships between local Nogo-B, plaque characteristics, and clinical data in patients undergoing carotid endarterectomy.
Methods and Results--Western blot analysis showed that endarterectomy specimens from the femoral (n=19) and carotid arteries (n=145) contained significantly less Nogo-B than nonatherosclerotic mammary arteries (n=8; P<0.003) and aortas (n=15; P=0.03). Immunohistochemistry revealed that in atherosclerotic lesions, Nogo-B was expressed by macrophage/foam cells, SMC rich, and neo-vascularized areas. Atheromatous plaques (>40% fat content) showed a significant reduction in Nogo-B expression (P=0.002). Nogo-B expression levels were significantly lower in patients with more than 90% of carotid stenosis (P=0.04) or restenotic lesions after prior carotid intervention (duplex; P=0.01). In contrast, plasmatic levels of Nogo-B (soluble Nogo-B) did not differ between atherosclerotic subjects (n=68) and risk-factor matched controls (n=63; P=0.5).
Conclusion--Our findings suggest that local reduction of Nogo-B in atherosclerotic tissue might contribute to plaque formation and/or instability triggering luminal narrowing. In contrast, plasma Nogo-B levels are not associated with clinically manifested atherosclerotic disease.
Key words: atherosclerosis • restenosis • vascular biology • Nogo-B
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