(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
This article has been cited by other articles:
 |
|
 |
|
  T. B. Grammer, W. Marz, W. Renner, B. O. Bohm, and M. M. Hoffmann C-reactive protein genotypes associated with circulating C-reactive protein but not with angiographic coronary artery disease: the LURIC study Eur. Heart J., May 21, 2008; (2008) ehn191v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Singh, M. R. Dasu, P. G. Yancey, A. Afify, S. Devaraj, and I. Jialal Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in Wistar rats J. Lipid Res., May 1, 2008; 49(5): 1015 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Singh, M. V. Suresh, D. C. Prayther, J. P. Moorman, A. E. Rusinol, and A. Agrawal C-Reactive Protein-Bound Enzymatically Modified Low-Density Lipoprotein Does Not Transform Macrophages into Foam Cells J. Immunol., March 15, 2008; 180(6): 4316 - 4322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. S. Packard and P. Libby Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction Clin. Chem., January 1, 2008; 54(1): 24 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Yamaleyeva, K. D. Pendergrass, N. T. Pirro, P. E. Gallagher, L. Groban, and M. C. Chappell Ovariectomy is protective against renal injury in the high-salt-fed older mRen2.Lewis rat Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2064 - H2071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Patel, C. A. King, S. R. Bailey, J. W. Holt, K. Venkatachalam, A. Agrawal, A. J. Valente, and B. Chandrasekar Interleukin-17 Stimulates C-reactive Protein Expression in Hepatocytes and Smooth Muscle Cells via p38 MAPK and ERK1/2-dependent NF-{kappa}B and C/EBPbeta Activation J. Biol. Chem., September 14, 2007; 282(37): 27229 - 27238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.C.Y. Yeung, A. Xu, C.W.S. Cheung, N.M.S. Wat, M.H. Yau, C.H.Y. Fong, M.T. Chau, and K.S.L. Lam Serum Adipocyte Fatty Acid-Binding Protein Levels Were Independently Associated With Carotid Atherosclerosis Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1796 - 1802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ryu, C. W. Lee, J.-A. Shin, C.-S. Park, J. J. Kim, S.-J. Park, and K. H. Han Fc{gamma}RIIa mediates C-reactive protein-induced inflammatory responses of human vascular smooth muscle cells by activating NADPH oxidase 4 Cardiovasc Res, August 1, 2007; 75(3): 555 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Palmerini, A. Marzocchi, C. Marrozzini, L. B. Reggiani, C. Savini, G. Marinelli, R. Di Bartolomeo, and A. Branzi Preoperative C-reactive protein levels predict 9-month mortality after coronary artery bypass grafting surgery for the treatment of left main coronary artery stenosis Eur. J. Cardiothorac. Surg., April 1, 2007; 31(4): 685 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Rocker, D. E. Manolov, E. V. Kuzmenkina, K. Tron, H. Slatosch, J. Torzewski, and G. U. Nienhaus Affinity of C-Reactive Protein toward Fc{gamma}RI Is Strongly Enhanced by the {gamma}-Chain Am. J. Pathol., February 1, 2007; 170(2): 755 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Blaschke, Y. Takata, E. Caglayan, A. Collins, P. Tontonoz, W. A. Hsueh, and R. K. Tangirala A Nuclear Receptor Corepressor-Dependent Pathway Mediates Suppression of Cytokine-Induced C-Reactive Protein Gene Expression by Liver X Receptor Circ. Res., December 8, 2006; 99(12): e88 - e99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Singh, S. Devaraj, M. R. Dasu, D. Ciobanu, J. Reusch, and I. Jialal C-Reactive Protein Decreases Interleukin-10 Secretion in Activated Human Monocyte-Derived Macrophages via Inhibition of Cyclic AMP Production Arterioscler. Thromb. Vasc. Biol., November 1, 2006; 26(11): 2469 - 2475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Juonala, J. S.A. Viikari, T. Ronnemaa, L. Taittonen, J. Marniemi, and O. T. Raitakari Childhood C-Reactive Protein in Predicting CRP and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1883 - 1888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Somani, P. J. Grant, K. Kain, A. J. Catto, and A. M. Carter Complement C3 and C-Reactive Protein Are Elevated in South Asians Independent of a Family History of Stroke Stroke, August 1, 2006; 37(8): 2001 - 2006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Paffen and M. P.M. deMaat C-reactive protein in atherosclerosis: A causal factor? Cardiovasc Res, July 1, 2006; 71(1): 30 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Guven, A. Cetinkaya, M. Aral, G. Sokmen, M. A. Buyukbese, A. Guven, and N. Koksal High-Sensitivity C-Reactive Protein in Patients with Metabolic Syndrome Angiology, May 1, 2006; 57(3): 295 - 302. [Abstract] [PDF]
|
|
|
|
 |
|
 C. R. BALISTRERI, S. VASTO, F. LISTI, M. P. GRIMALDI, D. LIO, G. COLONNA-ROMANO, M. CARUSO, G. CAIMI, E. HOFFMANN, C. CARUSO, et al. Association between +1059G/C CRP Polymorphism and Acute Myocardial Infarction in a Cohort of Patients from Sicily: A Pilot Study. Ann. N.Y. Acad. Sci., May 1, 2006; 1067: 276 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hermann and F. Ruschitzka Novel anti-inflammatory drugs in hypertension Nephrol. Dial. Transplant., April 1, 2006; 21(4): 859 - 864. [Full Text] [PDF]
|
|
|
|
 |
|
 K M J Douglas, A V Pace, G J Treharne, A Saratzis, P Nightingale, N Erb, M J Banks, and G D Kitas Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome Ann Rheum Dis, March 1, 2006; 65(3): 348 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Armstrong, D. A. Morrow, and M. S. Sabatine Inflammatory Biomarkers in Acute Coronary Syndromes: Part II: Acute-Phase Reactants and Biomarkers of Endothelial Cell Activation Circulation, February 21, 2006; 113(7): e152 - e155. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Can, S. Acikgoz, G. Mungan, T. Bayraktaroglu, E. Kocak, B. Guven, and S. Demirtas Serum cardiovascular risk factors in obstructive sleep apnea. Chest, February 1, 2006; 129(2): 233 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Soinio, J. Marniemi, M. Laakso, S. Lehto, and T. Ronnemaa High-Sensitivity C-Reactive Protein and Coronary Heart Disease Mortality in Patients With Type 2 Diabetes: A 7-year follow-up study Diabetes Care, February 1, 2006; 29(2): 329 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Meuwissen, A C van der Wal, H W M Niessen, K T Koch, R J de Winter, C M van der Loos, S Z H Rittersma, S A J Chamuleau, J G P Tijssen, A E Becker, et al. Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction J. Clin. Pathol., February 1, 2006; 59(2): 196 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wakugawa, Y. Kiyohara, Y. Tanizaki, M. Kubo, T. Ninomiya, J. Hata, Y. Doi, K. Okubo, Y. Oishi, K. Shikata, et al. C-Reactive Protein and Risk of First-Ever Ischemic and Hemorrhagic Stroke in a General Japanese Population: The Hisayama Study Stroke, January 1, 2006; 37(1): 27 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Y. Hsue and D. D. Waters What a Cardiologist Needs to Know About Patients With Human Immunodeficiency Virus Infection Circulation, December 20, 2005; 112(25): 3947 - 3957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Ciubotaru, L. A. Potempa, and R. C. Wander Production of Modified C-Reactive Protein in U937-Derived Macrophages Experimental Biology and Medicine, November 1, 2005; 230(10): 762 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Torzewski C-Reactive Protein and Atherogenesis: New Insights from Established Animal Models Am. J. Pathol., October 1, 2005; 167(4): 923 - 925. [Full Text] [PDF]
|
|
|
|
|
|
H. Sun, T. Koike, T. Ichikawa, K. Hatakeyama, M. Shiomi, B. Zhang, S. Kitajima, M. Morimoto, T. Watanabe, Y. Asada, et al. C-Reactive Protein in Atherosclerotic Lesions: Its Origin and Pathophysiological Significance Am. J. Pathol., October 1, 2005; 167(4): 1139 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fuster, P. R. Moreno, Z. A. Fayad, R. Corti, and J. J. Badimon Atherothrombosis and High-Risk Plaque: Part I: Evolving Concepts J. Am. Coll. Cardiol., September 20, 2005; 46(6): 937 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Trion, M.P.M. de Maat, J.W. Jukema, A. van der Laarse, M.C. Maas, E.H. Offerman, L.M. Havekes, A.J. Szalai, H.M.G. Princen, and J.J. Emeis No Effect of C-Reactive Protein on Early Atherosclerosis Development in Apolipoprotein E*3-Leiden/Human C-Reactive Protein Transgenic Mice Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1635 - 1640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Liu, S. Wang, A. Deb, K. A. Nath, Z. S. Katusic, J. P. McConnell, and N. M. Caplice Proapoptotic, Antimigratory, Antiproliferative, and Antiangiogenic Effects of Commercial C-Reactive Protein on Various Human Endothelial Cell Types In Vitro: Implications of Contaminating Presence of Sodium Azide in Commercial Preparation Circ. Res., July 22, 2005; 97(2): 135 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Arnaud, F. Burger, S. Steffens, N. R. Veillard, T. H. Nguyen, D. Trono, and F. Mach Statins Reduce Interleukin-6-Induced C-Reactive Protein in Human Hepatocytes: New Evidence for Direct Antiinflammatory Effects of Statins Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1231 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Di Napoli, M. Schwaninger, R. Cappelli, E. Ceccarelli, G. Di Gianfilippo, C. Donati, H. C.A. Emsley, S. Forconi, S. J. Hopkins, L. Masotti, et al. Evaluation of C-Reactive Protein Measurement for Assessing the Risk and Prognosis in Ischemic Stroke: A Statement for Health Care Professionals From the CRP Pooling Project Members Stroke, June 1, 2005; 36(6): 1316 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Qamirani, Y. Ren, L. Kuo, and T. W. Hein C-Reactive Protein Inhibits Endothelium-Dependent NO-Mediated Dilation in Coronary Arterioles by Activating p38 Kinase and NAD(P)H Oxidase Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 995 - 1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. Hilpert, P. M. Kris-Etherton, and S. G. West Lipid Response to a Low-Fat Diet with or without Soy Is Modified by C-Reactive Protein Status in Moderately Hypercholesterolemic Adults J. Nutr., May 1, 2005; 135(5): 1075 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. MacCallum Markers of Hemostasis and Systemic Inflammation in Heart Disease and Atherosclerosis in Smokers Proceedings of the ATS, April 1, 2005; 2(1): 34 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y Sato, K Hatakeyama, A Yamashita, K Marutsuka, A Sumiyoshi, and Y Asada Proportion of fibrin and platelets differs in thrombi on ruptured and eroded coronary atherosclerotic plaques in humans Heart, April 1, 2005; 91(4): 526 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. van Tits, J. de Graaf, H. Toenhake, W. van Heerde, and A. Stalenhoef C-Reactive Protein and Annexin A5 Bind to Distinct Sites of Negatively Charged Phospholipids Present in Oxidized Low-Density Lipoprotein Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 717 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Boekholdt, T. T. Keller, N. J. Wareham, R. Luben, S. A. Bingham, N. E. Day, M. S. Sandhu, J. W. Jukema, J. J.P. Kastelein, C. E. Hack, et al. Serum Levels of Type II Secretory Phospholipase A2 and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women: The EPIC-Norfolk Prospective Population Study Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 839 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bezzina Wettinger, C. J. M. Doggen, C. A. Spek, F. R. Rosendaal, and P. H. Reitsma High throughput mRNA profiling highlights associations between myocardial infarction and aberrant expression of inflammatory molecules in blood cells Blood, March 1, 2005; 105(5): 2000 - 2006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ivashchenko, F. Kramer, S. Schafer, A. Bucher, K. Veit, V. Hombach, A. Busch, O. Ritzeler, J. Dedio, and J. Torzewski Protein Kinase C Pathway Is Involved in Transcriptional Regulation of C-Reactive Protein Synthesis in Human Hepatocytes Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 186 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J.E. Sattler, J. E. Woodrum, O. Galili, M. Olson, S. Samee, F. B. Meyer, X.-Y. Zhu, L. O. Lerman, and A. Lerman Concurrent Treatment With Renin-Angiotensin System Blockers and Acetylsalicylic Acid Reduces Nuclear Factor {kappa}B Activation and C-Reactive Protein Expression in Human Carotid Artery Plaques Stroke, January 1, 2005; 36(1): 14 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Manolov, C. Rocker, V. Hombach, G. U. Nienhaus, and J. Torzewski Ultrasensitive Confocal Fluorescence Microscopy of C-Reactive Protein Interacting With Fc{gamma}RIIa Arterioscler. Thromb. Vasc. Biol., December 1, 2004; 24(12): 2372 - 2377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I B McInnes, D W McCarey, and N Sattar Do statins offer therapeutic potential in inflammatory arthritis? Ann Rheum Dis, December 1, 2004; 63(12): 1535 - 1537. [Full Text] [PDF]
|
|
|
|
|
|
S. Black, I. Kushner, and D. Samols C-reactive Protein J. Biol. Chem., November 19, 2004; 279(47): 48487 - 48490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P.M. de Maat, E. M. Bladbjerg, J. von Bornemann Hjelmborg, L. Bathum, J. Jespersen, and K. Christensen Genetic Influence on Inflammation Variables in the Elderly Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2168 - 2173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Okita, H. Nishijima, T. Murakami, T. Nagai, N. Morita, K. Yonezawa, K. Iizuka, H. Kawaguchi, and A. Kitabatake Can Exercise Training With Weight Loss Lower Serum C-Reactive Protein Levels? Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1868 - 1873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Blaschke, D. Bruemmer, F. Yin, Y. Takata, W. Wang, M. C. Fishbein, T. Okura, J. Higaki, K. Graf, E. Fleck, et al. C-Reactive Protein Induces Apoptosis in Human Coronary Vascular Smooth Muscle Cells Circulation, August 3, 2004; 110(5): 579 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Koh, M.-S. Shin, I. Sakuma, J. Y. Ahn, D. K. Jin, H. S. Kim, D. S. Kim, S. H. Han, W.-J. Chung, and E. K. Shin Effects of Conventional or Lower Doses of Hormone Replacement Therapy in Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1516 - 1521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F Tomai C reactive protein and microvascular function Heart, July 1, 2004; 90(7): 727 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Koh and I. Sakuma Should Progestins Be Blamed for the Failure of Hormone Replacement Therapy to Reduce Cardiovascular Events in Randomized Controlled Trials? Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1171 - 1179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.D. Waters and K.K. Khush Management of the acute coronary syndrome patient Eur. Heart J. Suppl., July 1, 2004; 6(suppl_C): C49 - C57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S.M. Shamsuzzaman, M. Winnicki, R. Wolk, A. Svatikova, B. G. Phillips, D. E. Davison, P. B. Berger, and V. K. Somers Independent Association Between Plasma Leptin and C-Reactive Protein in Healthy Humans Circulation, May 11, 2004; 109(18): 2181 - 2185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Paffen, H. L. Vos, and R. M. Bertina C-Reactive Protein Does Not Directly Induce Tissue Factor in Human Monocytes Arterioscler. Thromb. Vasc. Biol., May 1, 2004; 24(5): 975 - 981. [Abstract] [Full Text]
|
|
|
|
|
|
T. Khreiss, L. Jozsef, L. A. Potempa, and J. G. Filep Conformational Rearrangement in C-Reactive Protein Is Required for Proinflammatory Actions on Human Endothelial Cells Circulation, April 27, 2004; 109(16): 2016 - 2022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhakdi, M. Torzewski, K. Paprotka, S. Schmitt, H. Barsoom, P. Suriyaphol, S.-R. Han, K. J. Lackner, and M. Husmann Possible Protective Role for C-Reactive Protein in Atherogenesis: Complement Activation by Modified Lipoproteins Halts Before Detrimental Terminal Sequence Circulation, April 20, 2004; 109(15): 1870 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Schulze, E. B. Rimm, T. Li, N. Rifai, M. J. Stampfer, and F. B. Hu C-Reactive Protein and Incident Cardiovascular Events Among Men With Diabetes Diabetes Care, April 1, 2004; 27(4): 889 - 894. [Abstract] [Full Text] [PDF]
|
|