Response to Letter Regarding Article, “Human C-Reactive Protein Does Not Promote Atherosclerosis in Transgenic Rabbits”

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HomeCirculationVol. 122, No. 4Response to Letter Regarding Article, “Human C-Reactive Protein Does Not Promote Atherosclerosis in Transgenic Rabbits” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Letter Regarding Article, “Human C-Reactive Protein Does Not Promote Atherosclerosis in Transgenic Rabbits” Tomonari Koike, Ying Yu, Jifeng Zhang and Jianglin Fan Yukio Ozaki Shuji Kitajima and Kazutoshi Nishijima Masatoshi Morimoto Teruo Watanabe Sucharit Bhakdi Yujiro Asada Y. Eugene Chen Tomonari KoikeTomonari Koike Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan Search for more papers by this author , Ying YuYing Yu Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan Search for more papers by this author , Jifeng ZhangJifeng Zhang Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan Search for more papers by this author and Jianglin FanJianglin Fan Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan Search for more papers by this author Yukio OzakiYukio Ozaki Department of Clinical and Laboratory Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan Search for more papers by this author Shuji KitajimaShuji Kitajima Analytical Research Center for Experimental Sciences, Saga University, Saga, Japan Search for more papers by this author and Kazutoshi NishijimaKazutoshi Nishijima Analytical Research Center for Experimental Sciences, Saga University, Saga, Japan Search for more papers by this author Masatoshi MorimotoMasatoshi Morimoto Department of Rehabilitation, Kumamoto Health Science University, Kumamoto, Japan Search for more papers by this author Teruo WatanabeTeruo Watanabe Fukuoka Wajiro Hospital, Fukuoka, Japan Search for more papers by this author Sucharit BhakdiSucharit Bhakdi Institute of Medical Microbiology and Hygiene, Mainz, Germany Search for more papers by this author Yujiro AsadaYujiro Asada The First Department of Pathology, Faculty of Medicine, Miyazaki University, Miyazaki, Japan Search for more papers by this author Y. Eugene ChenY. Eugene Chen Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Mich Search for more papers by this author Originally published27 Jul 2010https://doi.org/10.1161/CIRCULATIONAHA.110.951798Circulation. 2010;122:e407We appreciate the comments by Nakajima and Saito on our recent article published in Circulation.1 The major question they raised was why human C-reactive protein (CRP) transgenic rabbits failed to exhibit other metabolic disorders, because emerging data support that CRP levels are elevated in patients with metabolic syndrome.2 It is well documented that elevated plasma CRP levels are associated with many pathological states such as cardiovascular diseases and metabolic syndrome; however, these associations do not necessarily mean that high levels of CRP can cause these diseases. Indeed, population genetics studies have failed to link CRP single-nucleotide polymorphisms to the increased risk of cardiovascular diseases, although CRP single-nucleotide polymorphisms are associated with marked increases in CRP levels.3,4 Also, there is no evidence to date to show that elevation of plasma CRP alone can lead to metabolic syndrome both clinically and experimentally. It is apparent that further experiments with appropriate large-animal models are required to investigate CRP functions in metabolic syndrome. Because metabolic syndrome is composed of several metabolic disorders (eg, hypertension, dyslipidemia, and hyperglycemia), which are mediated by multiple genes and many environmental factors, it is unlikely that overexpression of a single CRP gene in animals can lead to all these abnormalities. In fact, we have recently transgenically expressed human CRP in hypertensive animals and found that in the setting of hypertension, CRP does exert certain detrimental effects on both lipid and glucose metabolism (unpublished data). Taken together, CRP functions in both physiology and pathophysiology remain to be further elucidated with genetically modified large animals, as we reported in the study.1DisclosuresNone. References 1 Koike T, Kitajima S, Yu Y, Nishijima K, Zhang J, Ozaki Y, Morimoto M, Watanabe T, Bhakdi S, Asada Y, Chen YE, Fan J. Human C-reactive protein does not promote atherosclerosis in transgenic rabbits. Circulation. 2009; 120: 2088–2094.LinkGoogle Scholar2 Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation. 2003; 107: 391–397.LinkGoogle Scholar3 Wang Q, Hunt SC, Xu Q, Chen YE, Province MA, Eckfeldt JH, Pankow JS, Song Q. Association study of CRP gene polymorphisms with serum CRP level and cardiovascular risk in the NHLBI Family Heart Study. Am J Physiol Heart Circ Physiol. 2006; 291: H2752–H2757.CrossrefMedlineGoogle Scholar4 Zacho J, Tybjaerg-Hansen A, Jensen JS, Grande P, Sillesen H, Nordestgaard BG. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med. 2008; 359: 1897–1908.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 27, 2010Vol 122, Issue 4 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.110.951798 Originally publishedJuly 27, 2010 PDF download Advertisement SubjectsAnimal Models of Human DiseaseEpidemiologyMechanismsPathophysiology