Selective apheresis of C-reactive protein: A new therapeutic option in myocardial infarction?
Corresponding Author
Ahmed Sheriff
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Ahmed Sheriff and Ralf Schindler contributed equally to this work.
Correspondence to: Ahmed Sheriff, Charité—Universitätsmedizin Berlin, Hessische Str. 3–4, 10115 Berlin, Germany. E-mail: [email protected]Search for more papers by this authorRalf Schindler
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Ahmed Sheriff and Ralf Schindler contributed equally to this work.
Search for more papers by this authorBirgit Vogt
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorHassan Abdel-Aty
Cardiac MRI Team, Franz-Volhard-Klinik, Charité – Universitätsmedizin Berlin, Helios Kliniken, Berlin Buch, Germany
Search for more papers by this authorJuliane K. Unger
Department of Experimental Medicine, Charité – Universitätsmedizin Berlin, Berlin Germany
Search for more papers by this authorChristopher Bock
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorFrank Gebauer
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorAnna Slagman
Department of Cardiology, Charité – Universitätsmedizin Berlin, Germany
Search for more papers by this authorTimo Jerichow
Department of Cardiology, Charité – Universitätsmedizin Berlin, Germany
Search for more papers by this authorDörte Mans
Department of Cardiology, Charité – Universitätsmedizin Berlin, Germany
Search for more papers by this authorGülcan Yapici
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorGunnar Janelt
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorMalte Schröder
Department of Cardiology, Charité – Universitätsmedizin Berlin, Germany
Search for more papers by this authorRudolf Kunze
Office Campus Max Delbrück Centrum, Berlin, Germany
Search for more papers by this authorMartin Möckel
Department of Cardiology, Charité – Universitätsmedizin Berlin, Germany
Search for more papers by this authorCorresponding Author
Ahmed Sheriff
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Ahmed Sheriff and Ralf Schindler contributed equally to this work.
Correspondence to: Ahmed Sheriff, Charité—Universitätsmedizin Berlin, Hessische Str. 3–4, 10115 Berlin, Germany. E-mail: [email protected]Search for more papers by this authorRalf Schindler
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Ahmed Sheriff and Ralf Schindler contributed equally to this work.
Search for more papers by this authorBirgit Vogt
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorHassan Abdel-Aty
Cardiac MRI Team, Franz-Volhard-Klinik, Charité – Universitätsmedizin Berlin, Helios Kliniken, Berlin Buch, Germany
Search for more papers by this authorJuliane K. Unger
Department of Experimental Medicine, Charité – Universitätsmedizin Berlin, Berlin Germany
Search for more papers by this authorChristopher Bock
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorFrank Gebauer
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorAnna Slagman
Department of Cardiology, Charité – Universitätsmedizin Berlin, Germany
Search for more papers by this authorTimo Jerichow
Department of Cardiology, Charité – Universitätsmedizin Berlin, Germany
Search for more papers by this authorDörte Mans
Department of Cardiology, Charité – Universitätsmedizin Berlin, Germany
Search for more papers by this authorGülcan Yapici
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorGunnar Janelt
Department of Nephrology and Internal Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
Search for more papers by this authorMalte Schröder
Department of Cardiology, Charité – Universitätsmedizin Berlin, Germany
Search for more papers by this authorRudolf Kunze
Office Campus Max Delbrück Centrum, Berlin, Germany
Search for more papers by this authorMartin Möckel
Department of Cardiology, Charité – Universitätsmedizin Berlin, Germany
Search for more papers by this authorAbstract
Background: There is substantial evidence that C-reactive protein (CRP) mediates secondary damage of the myocardium after acute myocardial infarction (AMI). The aim of this animal trial in pigs was to specifically deplete CRP from porcine plasma after AMI and to study possible beneficial effects of the reduced CRP concentration on the infarcted area. Methods: Ten pigs received balloon catheter-induced myocardial infarction. CRP was depleted from five animals utilizing a new specific CRP-adsorber, five animals served as controls. The area of infarction was analyzed by cardiovascular magnetic resonance imaging on day 1 and day 14 after AMI. Porcine CRP levels were determined by ELISA. Results: CRP-apheresis resulted in a mean reduction of the CRP levels up to 48.3%. The area of infarction was significantly reduced by 30 ± 6% (P = 0.003) within 14 days in the treatment group, whereas it increased by 19 ± 11% (P = 0.260) in the controls. Fourteen days after infarction, the infarcted area revealed compact, transmural scars in the controls, whereas animals receiving CRP-apheresis showed spotted scar morphology. In the interventional group, a significantly higher left ventricular ejection fraction (LVEF) was observed after 14 days as compared to the controls (57.6 ± 2.4% vs. 46.4 ± 2.7%; P = 0.007). Conclusions: In a pig model for AMI, we observed that selective CRP-apheresis significantly reduces CRP levels and the volume of the infarction zone after AMI. Additionally, it changes the morphology of the scars and preserves cardiac output (LVEF). J. Clin. Apheresis 30:15–21, 2015. © 2014 Wiley Periodicals, Inc.
REFERENCES
- 1Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest 2003; 111: 1805-1812.
- 2Casas JP, Shah T, Hingorani AD, Danesh J, Pepys MB. C-reactive protein and coronary heart disease: a critical review. J Intern Med 2008; 264: 295-314.
- 3Volanakis JE. Human C-reactive protein: expression, structure, and function. Mol Immunol 2001; 38: 189-197.
- 4Biasucci LM, Liuzzo G, Grillo RL, Caligiuri G, Rebuzzi AG, Buffon A, Summaria F, Ginnetti F, Fadda G, Maseri A. Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 1999; 99: 855-860.
- 5Bursi F, Weston SA, Killian JM, Gabriel SE, Jacobsen SJ, Roger VL. C-reactive protein and heart failure after myocardial infarction in the community. Am J Med 2007; 120: 616-622.
- 6Kavsak PA, MacRae AR, Newman AM, Lustig V, Palomaki GE, Ko DT, Tu JV, Jaffe AS. Elevated C-reactive protein in acute coronary syndrome presentation is an independent predictor of long-term mortality and heart failure. Clin Biochem 2007; 40: 326-329.
- 7Kinjo K, Sato H, Ohnishi Y, Hishida E, Nakatani D, Mizuno H, Imai K, Nanto S, Naka M, Matsumura Y, Takeda H, Hori M. Impact of high-sensitivity C-reactive protein on predicting long-term mortality of acute myocardial infarction. Am J Cardiol 2003; 91: 931-935.
- 8Pietilä KO, Harmoinen AP, Jokiniitty J, Pasternack AI. Serum C-reactive protein concentration in acute myocardial infarction and its relationship to mortality during 24 months of follow-up in patients under thrombolytic treatment. Eur Heart J 1996; 17: 1345-1349.
- 9Suleiman M, Aronson D, Reisner SA, Kapeliovich MR, Markiewicz W, Levy Y, Hammerman H. Admission C-reactive protein levels and 30-day mortality in patients with acute myocardial infarction. Am J Med 2003; 115: 695-701.
- 10Suleiman M, Khatib R, Agmon Y, Mahamid R, Boulos M, Kapeliovich M, Levy Y, Beyar R, Markiewicz W, Hammerman H, Aronson D. Early inflammation and risk of long-term development of heart failure and mortality in survivors of acute myocardial infarction predictive role of C-reactive protein. J Am Coll Cardiol 2006; 47: 962-968.
- 11Dimitrijevic O, Stojcevski BD, Ignjatovic S, Singh NM. Serial measurements of C-reactive protein after acute myocardial infarction in predicting one-year outcome. Int Heart J 2006; 47: 833-842.
- 12Berton G, Cordiano R, Palmieri R, Pianca S, Pagliara V, Palatini P. C-reactive protein in acute myocardial infarction: association with heart failure. Am Heart J 2003; 145: 1094-1101.
- 13Anzai T, Yoshikawa T, Shiraki H, Asakura Y, Akaishi M, Mitamura H, Ogawa S. C-reactive protein as a predictor of infarct expansion and cardiac rupture after a first Q-wave acute myocardial infarction. Circulation 1997; 96: 778-784.
- 14Barrett TD, Hennan JK, Marks RM, Lucchesi BR. C-reactive-protein-associated increase in myocardial infarct size after ischemia/reperfusion. J Pharmacol Exp Ther 2002; 303: 1007-1013.
- 15Griselli M, Herbert J, Hutchinson WL, Taylor KM, Sohail M, Krausz T, Pepys MB. C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med 1999; 190: 1733-1740.
- 16Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, Hawkins PN, Myers RM, Smith MD, Polara A, Cobb AJA, Ley SV, Aquilina JA, Robinson CV, Sharif I, Gray GA, Sabin CA, Jenvey MC, Kolstoe SE, Thompson D, Wood SP. Targeting C-reactive protein for the treatment of cardiovascular disease. Nature 2006; 440: 1217-1221.
- 17Kitsis RN, Jialal I. Limiting myocardial damage during acute myocardial infarction by inhibiting C-reactive protein. N Engl J Med 2006; 355: 513-515.
- 18Slagman AC, Bock C, Abdel-Aty H, Vogt B, Gebauer F, Janelt G, Wohlgemuth F, Morgenstern R, Yapici G, Puppe A, Modersohn D, Mans D, Jerichow T, Ott S, Kunze R, Schrödl W, Janko C, Hermann M, Kalden JR, Kern P, Parsch H, Kirschfink M, Schulz-Menger J, Röttgen R, Unger JK, Frei U, Schindler R, Möckel M, Sheriff A. Specific removal of C-reactive protein by apheresis in a porcine cardiac infarction model. Blood Purif 2011; 31: 9-17.
- 19Ertl G, Frantz S. Healing after myocardial infarction. Cardiovasc Res 2005; 66: 22-32.
- 20Takemura G, Nakagawa M, Kanamori H, Minatoguchi S, Fujiwara H. Benefits of reperfusion beyond infarct size limitation. Cardiovasc Res 2009; 83: 269-276.
- 21Brunetti ND, Correale M, Pellegrino PL, Cuculo A, Biase MD. Acute phase proteins in patients with acute coronary syndrome: Correlations with diagnosis, clinical features, and angiographic findings. Eur J Intern Med 2007; 18: 109-117.
- 22Hashemi SM, Ghods S, Kolodgie FD, Parcham-Azad K, Keane M, Hamamdzic D, Young R, Rippy MK, Virmani R, Litt H, Wilensky RL. A placebo controlled, dose-ranging, safety study of allogenic mesenchymal stem cells injected by endomyocardial delivery after an acute myocardial infarction. Eur Heart J 2008; 29: 251-259.
- 23Jacquier A, Higgins CB, Martin AJ, Do L, Saloner D, Saeed M. Injection of adeno-associated viral vector encoding vascular endothe
- 24Mahnken AH, Bruners P, Kinzel S, Katoh M, Muhlenbruch G, et al. Late-phase MSCT in the different stages of myocardial infarction: animal experiments. Eur Radiol 2007; 17: 2310–2317.
- 25Saeed M, Martin A, Ursell P, Do L, Bucknor M, et al. MR assessment of myocardial perfusion, viability, and function after intramyocardial transfer of VM202, a new plasmid human hepatocyte growth factor in ischemic swine myocardium. Radiology 2008; 249: 107–118.
- 26Hack CE, Niessen HW. Cardiovascular secrets of secretory phospholipase A(2). Eur J Clin Invest 2002; 32: 381–382.
- 27Krijnen PA, Meischl C, Nijmeijer R, Visser CA, Hack CE, et al. Inhibition of sPLA2-IIA, C-reactive protein or complement: new therapy for patients with acute myocardial infarction? Cardiovasc Hematol Disord Drug Targets 2006; 6: 113–123.
- 28Nijmeijer R, Lagrand WK, Baidoshvili A, Lubbers YT, Hermens WT, et al. Secretory type II phospholipase A(2) binds to ischemic myocardium during myocardial infarction in humans. Cardiovasc Res 2002; 53: 138–146.
- 29Nijmeijer R, Willemsen M, Meijer CJ, Visser CA, Verheijen RH, et al. Type II secretory phospholipase A2 binds to ischemic flip-flopped cardiomyocytes and subsequently induces cell death. Am J Physiol Heart Circ Physiol 2003; 285: H2218–H2224.
- 30Kudo I, Murakami M. Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat 2002; 68–69: 3–58.
- 31Gershov D, Kim S, Brot N, Elkon KB. C-Reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 2000; 192: 1353–1364.
- 32Mevorach D, Mascarenhas JO, Gershov D, Elkon KB. Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 1998; 88: 2313–2320.
Citing Literature
