Human Carotid Plaque Calcification and Vulnerability
Relationship between Degree of Plaque Calcification, Fibrous Cap Inflammatory Gene Expression and SymptomatologyWahlgren C.-M. · Zheng W. · Shaalan W. · Tang J. · Bassiouny H.S.
Section of Vascular Surgery, Department of Surgery, University of Chicago, Chicago, Ill., USA Cerebrovasc Dis 2009;27:193–200 (DOI:10.1159/000189204)
Background: Inflammation is a key mechanism in human atherosclerotic plaque vulnerability and disruption. The objective was to determine the differential gene expression of pro- and anti-inflammatory factors in the fibrous cap and shoulder region of noncalcified and calcified carotid endarterectomy plaques. Methods: Thirty carotid endarterectomy plaques were classified as type Va (noncalcified, n = 15) and type Vb (calcified, n = 15) in accordance with the American Heart Association consensus. Using laser capture microdissection, fibrous cap and shoulder regions were excisedfrom frozen sections. Gene expression of pro- [interleukin 1 (IL-1), IL-8 and monocyte chemoattractant protein 1 (MCP-1)] and anti-inflammatory (IL-10) factors, and bone formation (bone morphogenetic protein 6 and osteocalcin) mediators were quantitated by real-time PCR. Protein levels were determined using Western blotting. Results: Mean percent carotid stenosis and calcification area were 79 and 5% in Va-plaques (40% symptomatic) and 77 and 42% in Vb-plaques (20% symptomatic). Macrophages infiltrating the region of the fibrous cap and the shoulder were more numerous in non-calcified plaques compared with calcified plaques (p < 0.01]. mRNA expression of MCP-1 and IL-8, and protein levels of IL-8 were also greater in Va plaques compared to Vb plaques (p < 0.05). Protein levels and mRNA expression of osteocalcin were greater in Vb compared to Va plaques (p < 0.05). Conclusions: Fibrous cap inflammation is more likely to occur in noncalcified than in calcified plaques. These findings suggest that carotid atherosclerotic plaque calcification is a structural marker of plaque stability.
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