C-reactive protein in atherosclerotic lesions: its origin and pathophysiological significance.
C-reactive protein (CRP) is frequently deposited in the lesions of the arterial intima; however, the origin and pathological significance of CRP in these lesions are not completely understood. In this study, we measured CRP levels in the plasma of hypercholesterolemic rabbits and investigated CRP expression at both the mRNA and protein levels using rabbit and human atherosclerotic specimens. CRP levels were significantly elevated in both cholesterol-fed and Watanabe heritable hyperlipidemic rabbits, and CRP levels were clearly correlated with aortic atherosclerotic lesion size. Immunohistochemical staining coupled with Western blotting analysis revealed that CRP-immunoreactive proteins were found at all stages of atherosclerosis from the early to advanced lesions. CRP was present extracellularly and co-localized with apolipoprotein B but was rarely associated with the cytoplasm of macrophages and foam cells. Real-time reverse transcriptase-polymerase chain reaction analysis revealed that CRP mRNA in atherosclerotic lesions was barely detectable, and isolated macrophages did not express CRP mRNA, suggesting that CRP proteins found in the lesions were essentially derived from the circulation rather than synthesized de novo by vascular cells. These results suggest that there is a link between plasma CRP and the degree of atherosclerosis and that inhibition of plasma CRP may represent a therapeutic modality for the treatment of cardiovascular disease.
Sun
Huijun
H
Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
Koike
Tomonari
T
Ichikawa
Tomonaga
T
Hatakeyama
Kinta
K
Shiomi
Masashi
M
Zhang
Bo
B
Kitajima
Shuji
S
Morimoto
Masatoshi
M
Watanabe
Teruo
T
Asada
Yujiro
Y
Chen
Yuqing E
YE
Fan
Jianglin
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001011:Aorta / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000633:toxicity; D003331:Coronary Vessels / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms
D000911:Antibodies, Monoclonal; D002791:Cholesterol, Dietary; D012333:RNA, Messenger; D002097:C-Reactive Protein