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Title: C-REACTIVE PROTEIN CORRELATES WITH MACROPHAGE ACCUMULATION IN CORONARY ARTERIES IN PIGS FED A HIGH FAT AND CHOLESTEROL DIET

Author
item TURK, JAMES - UNIV OF MISSOURI-COLUMBIA
item Carroll, Jeffery - Jeff Carroll
item LAUGHLIN, HAROLD - UNIV OF MISSOURI-COLUMBIA
item THOMAS, TOM - UNIV OF MISSOURI-COLUMBIA
item STUREK, MICHAEL - UNIV OF MISSOURI-COLUMBIA
item BOWLES, DOUGLAS - UNIV OF MISSOURI-COLUMBIA
item CASATI, JENNIFER - UNIV OF MISSOURI-COLUMBIA

Submitted to: Journal of Applied Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/6/2003
Publication Date: 5/16/2003
Citation: TURK, J.R., CARROLL, J.A., LAUGHLIN, H.M., THOMAS, T.R., STUREK, M., BOWLES, D.K., CASATI, J. C-REACTIVE PROTEIN CORRELATES WITH MACROPHAGE ACCUMULATION IN CORONARY ARTERIES IN PIGS FED A HIGH FAT AND CHOLESTEROL DIET. JOURNAL OF APPLIED PHYSIOLOGY. 2003. V. 95. P. 1301-1304.

Interpretive Summary: A study was conducted utilizing the pig model to test the hypothesis that serum C-reactive protein (CRP) correlates with the accumulation of certain immune cells in coronary artery disease. Pigs were fed a normal chow (N) or a high fat-high cholesterol (HF) diet to induce hypercholesterolemia. The data revealed that there was a high, positive correlation between serum CRP and cholesterol, and the accumulation of immune cells in the coronary arteries of pigs with diet-induced hypercholesterolemia. Imaging results revealed that CRP was co-localized with other inflammatory markers in the cells of coronary arteries from hypercholesterolemic pigs. These results support a role for CRP in the pathogenesis of coronary artery disease. Thus, we conclude that our results are consistent with the proposal that CRP correlates with the accumulation of immune cells during the development of coronary artery disease and that elevated serum CRP may be a risk factor for coronary artery disease. The results of this study will be of particular interest to nutritional scientists investigating the effects of a high fat diet on the development of coronary artery disease. Additionally, scientists working in the area of stress physiology and immunology will be interested in the correlations between CRP and the development of coronary artery disease.

Technical Abstract: A growing body of evidence supports the hypothesis that C-reactive protein (CRP) is a marker of coronary artery disease. In the current study, 16 adult male Yucatan pigs were fed a normal chow (N) or a high fat-high cholesterol (HF) diet. Blood was collected for analyses of CRP and lipids. At week 20, the pigs were euthanized and the right coronary arteries were harvested and fixed in neutral buffered formalin. Paraffin-embedded sections of right coronary arteries were stained immunohistochemically for CRP, scavenger receptor A, and monocyte chemoattractant protein 1. All cholesterol fractions were elevated in the HF vs. N groups (P<0.05). There was little or no positive staining for CRP, scavenger receptor A, or monocyte chemoattractant protein 1 in the right coronary arteries of N pigs, but extensive staining was observed in lipid-laden macrophage foam cells in the HF pigs. Double staining revealed co-localization of CRP with scavenger receptor A and CRP with monocyte chemoattractant protein 1 in foam cells. Serum CRP correlated directly with plasma total cholesterol (R=0.727, P=0.041) and accumulation of scavenger receptor A-positive macrophages (R=0.938, P<0.001) in the right coronary arteries of HF pigs. These data demonstrate that serum CRP correlates with macrophage accumulation and coronary artery disease in pigs fed a HF diet.