(Circulation. 2001;103:1194.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
C-Reactive Protein–Mediated Low Density Lipoprotein Uptake by Macrophages
Implications for Atherosclerosis
From Internal Medicine II–Cardiology, University of Ulm, Ulm, Germany.
Correspondence to Jan Torzewski, MD, MPhil, Internal Medicine II, Cardiology, University of Ulm, Robert Koch-Str 8, 89081 Ulm, Germany. E-mail jan.torzewski{at}medizin.uni-ulm.de
Background—LDL and C-reactive protein (CRP) are important cardiovascular risk factors. Both LDL and CRP deposit in the arterial wall during atherogenesis. Stranded LDL is taken up by macrophages, causing foam cell formation. Because native LDL does not induce foam cell formation, we hypothesized that CRP may opsonize native LDL for macrophages.
Methods and Results—Monocytes were isolated from human blood and transformed into macrophages. CRP/LDL uptake was assessed by immunofluorescent labeling and the use of confocal laser scanning microscopy. Native LDL coincubated with CRP was taken up by macrophages by macropinocytosis. Uptake of the CRP/LDL coincubate was mediated by the CRP receptor CD32.
Conclusions—We conclude that foam cell formation in human atherogenesis may be caused in part by uptake of CRP-opsonized native LDL.
Key Words: lipids • C-reactive protein • atherosclerosis
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H. K. Meier-Ewert, P. M. Ridker, N. Rifai, M. M. Regan, N. J. Price, D. F. Dinges, and J. M. Mullington Effect of sleep loss on C-Reactive protein, an inflammatory marker of cardiovascular risk J. Am. Coll. Cardiol., February 18, 2004; 43(4): 678 - 683. [Abstract] [Full Text] [PDF]
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A. Paul, K. W.S. Ko, L. Li, V. Yechoor, M. A. McCrory, A. J. Szalai, and L. Chan C-Reactive Protein Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice Circulation, February 10, 2004; 109(5): 647 - 655. [Abstract] [Full Text] [PDF]
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P. Y. Hsue, K. Giri, S. Erickson, J. S. MacGregor, N. Younes, A. Shergill, and D. D. Waters Clinical Features of Acute Coronary Syndromes in Patients With Human Immunodeficiency Virus Infection Circulation, January 27, 2004; 109(3): 316 - 319. [Abstract] [Full Text] [PDF]
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S. Verma and P. E. Szmitko Coxibs and the endothelium J. Am. Coll. Cardiol., November 19, 2003; 42(10): 1754 - 1756. [Full Text] [PDF]
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P. M Ridker and on behalf of the JUPITER Study Group Rosuvastatin in the Primary Prevention of Cardiovascular Disease Among Patients With Low Levels of Low-Density Lipoprotein Cholesterol and Elevated High-Sensitivity C-Reactive Protein: Rationale and Design of the JUPITER Trial* Circulation, November 11, 2003; 108(19): 2292 - 2297. [Full Text] [PDF]
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R. Wolk, P. Berger, R. J. Lennon, E. S. Brilakis, and V. K. Somers Body Mass Index: A Risk Factor for Unstable Angina and Myocardial Infarction in Patients With Angiographically Confirmed Coronary Artery Disease Circulation, November 4, 2003; 108(18): 2206 - 2211. [Abstract] [Full Text] [PDF]
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A. Silvestro, F. Scopacasa, A. Ruocco, G. Oliva, V. Schiano, C. Zincarelli, and G. Brevetti Inflammatory status and endothelial function in asymptomatic and symptomatic peripheral arterial disease Vascular Medicine, November 1, 2003; 8(4): 225 - 232. [Abstract] [PDF]
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S. B. Schwedler, F. Guderian, J. Dammrich, L. A. Potempa, and C. Wanner Tubular staining of modified C-reactive protein in diabetic chronic kidney disease Nephrol. Dial. Transplant., November 1, 2003; 18(11): 2300 - 2307. [Abstract] [Full Text] [PDF]
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 G.M. Hirschfield and M.B. Pepys C-reactive protein and cardiovascular disease: new insights from an old molecule QJM, November 1, 2003; 96(11): 793 - 807. [Abstract] [Full Text] [PDF]
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 G. J. Blake and P. M. Ridker C-reactive protein: a surrogate risk marker or mediator of atherothrombosis? Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2003; 285(5): R1250 - R1252. [Full Text] [PDF]
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S. Verma, M. R. Buchanan, and T. J. Anderson Endothelial Function Testing as a Biomarker of Vascular Disease Circulation, October 28, 2003; 108(17): 2054 - 2059. [Full Text] [PDF]
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 B. OSTERUD and E. BJORKLID Role of Monocytes in Atherogenesis Physiol Rev, October 1, 2003; 83(4): 1069 - 1112. [Abstract] [Full Text] [PDF]
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K. K. Koh, J. Y. Ahn, D. K. Jin, B.-K. Yoon, H. S. Kim, D. S. Kim, W. C. Kang, S. H. Han, I. S. Choi, and E. K. Shin Significant Differential Effects of Hormone Therapy or Tibolone on Markers of Cardiovascular Disease in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Arterioscler Thromb Vasc Biol, October 1, 2003; 23(10): 1889 - 1894. [Abstract] [Full Text] [PDF]
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 A. P. Miller, Y.-F. Chen, D. Xing, W. Feng, and S. Oparil Hormone Replacement Therapy and Inflammation: Interactions in Cardiovascular Disease Hypertension, October 1, 2003; 42(4): 657 - 663. [Abstract] [Full Text] [PDF]
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W. J. Jabs, E. Theissing, M. Nitschke, J.F. M. Bechtel, M. Duchrow, S. Mohamed, B. Jahrbeck, H.-H. Sievers, J. Steinhoff, and C. Bartels Local Generation of C-Reactive Protein in Diseased Coronary Artery Venous Bypass Grafts and Normal Vascular Tissue Circulation, September 23, 2003; 108(12): 1428 - 1431. [Abstract] [Full Text] [PDF]
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 D. G. Hackam and S. S. Anand Emerging Risk Factors for Atherosclerotic Vascular Disease: A Critical Review of the Evidence JAMA, August 20, 2003; 290(7): 932 - 940. [Abstract] [Full Text] [PDF]
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S. Kobayashi, N. Inoue, Y. Ohashi, M. Terashima, K. Matsui, T. Mori, H. Fujita, K. Awano, K. Kobayashi, H. Azumi, et al. Interaction of Oxidative Stress and Inflammatory Response in Coronary Plaque Instability: Important Role of C-Reactive Protein Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1398 - 1404. [Abstract] [Full Text] [PDF]
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J. J. Cao, C. Thach, T. A. Manolio, B. M. Psaty, L. H. Kuller, P. H.M. Chaves, J. F. Polak, K. Sutton-Tyrrell, D. M. Herrington, T. R. Price, et al. C-Reactive Protein, Carotid Intima-Media Thickness, and Incidence of Ischemic Stroke in the Elderly: The Cardiovascular Health Study Circulation, July 15, 2003; 108(2): 166 - 170. [Abstract] [Full Text] [PDF]
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C.-H. Wang, S.-H. Li, R. D. Weisel, P. W.M. Fedak, A. S. Dumont, P. Szmitko, R.-K. Li, D. A.G. Mickle, and S. Verma C-Reactive Protein Upregulates Angiotensin Type 1 Receptors in Vascular Smooth Muscle Circulation, April 8, 2003; 107(13): 1783 - 1790. [Abstract] [Full Text] [PDF]
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A. W. Chan, D. L. Bhatt, D. P. Chew, J. Reginelli, J. P. Schneider, E. J. Topol, and S. G. Ellis Relation of Inflammation and Benefit of Statins After Percutaneous Coronary Interventions Circulation, April 8, 2003; 107(13): 1750 - 1756. [Abstract] [Full Text] [PDF]
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Y. Hattori, M. Matsumura, and K. Kasai Vascular smooth muscle cell activation by C-reactive protein Cardiovasc Res, April 1, 2003; 58(1): 186 - 195. [Abstract] [Full Text] [PDF]
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D. D. Sin and S.F. P. Man Why Are Patients With Chronic Obstructive Pulmonary Disease at Increased Risk of Cardiovascular Diseases?: The Potential Role of Systemic Inflammation in Chronic Obstructive Pulmonary Disease Circulation, March 25, 2003; 107(11): 1514 - 1519. [Abstract] [Full Text] [PDF]
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S.C. Kofoed, H.H. Wittrup, H. Sillesen, and B.G. Nordestgaard Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques: The Copenhagen City Heart Study Eur. Heart J., March 2, 2003; 24(6): 567 - 576. [Abstract] [Full Text] [PDF]
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G. J. Blake and P. M. Ridker C-reactive protein and other inflammatory risk markers in acute coronary syndromes J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 37S - 42S. [Abstract] [Full Text] [PDF]
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