Journal of Applied Physiology
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J Appl Physiol (May 16, 2003). doi:10.1152/japplphysiol.00342.2003
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Submitted on April 7, 2003
Accepted on May 8, 2003

C-reactive Protein Correlates with Macrophage Accumulation in Coronary Arteries of Hypercholesterolemic Pigs

James R Turk1*, Jeffery A Carroll2, M. Harold Laughlin3, Tom R Thomas4, Jennifer Casati1, Douglas K Bowles3, and Michael Sturek5

1 Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA
2 Animal Physiology Research Unit, ARS-USDA, University of Missouri, Columbia, Missouri, USA
3 Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA; Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, USA
4 Department of Nutritional Sciences, University of Missouri, Columbia, Missouri, USA
5 Departments of Medical Pharamacology & Physiology and Internal Medicine, University of Missouri, Columbia, Missouri, USA

* To whom correspondence should be addressed. E-mail: turkj{at}missouri.edu.

A growing body of evidence supports the hypothesis that C-reactive protein (CRP) is a marker of inflammation in coronary artery disease. The purpose of the present study was to test the hypothesis that CRP correlates with macrophage accumulation during the initial stages of coronary vascular disease. Adult male pigs were fed a normal chow (N) or high fat high cholesterol (HF) diet for a 20-week period. At week 20, blood was collected for analyses of interleukin-6 (IL-6), CRP, and lipids. Following blood collection, the pigs were euthanized and the right coronary arteries (RCA) were harvested and fixed in neutral buffered formalin. Paraffin-embedded sections of RCA were stained immunohistochemically for CRP, scavenger receptor A (SRA), and monocyte chemoattractant protein 1 (MCP-1). All cholesterol fractions were elevated in the HF versus N groups (P<0.05). There was little or no positive staining for CRP, SRA, or MCP-1 in the RCA of N pigs, but extensive staining in lipid-laden macrophage foam cells in the HF pigs. Double staining revealed colocalization of CRP with SRA and CRP with MCP-1 in foam cells. Serum IL-6 was below the assay detection limit in all pigs. Serum CRP correlated directly with plasma total cholesterol (R=0.727, P=0.041) and accumulation of SRA-positive macrophages (R=0.938, P<0.001) in the RCA of HF pigs. We conclude that serum CRP correlates with macrophage accumulation and coronary artery disease in hypercholesterolemic pigs.




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