Makrophagenstoffwechsel

Ziel unserer Forschung ist es, den Prozeß der Schaumzellbildung anhand eines in vitro Modells näher zu charakterisieren, um diesen Prozeß in vivo besser zu verstehen und mögliche therapeutische Ansatzpünkte zu erkennen. Hierzu gehören die Untersuchung der Genregulation in Schaumzellen mittels PCR Differential Display und Genchip-Analyse, die Erforschung des Cholesterin- und ApoE-Stoffwechsels des Makrophagen und der Schaumzelle, die Erkundung der Schaumzellbildung mittels Aufnahme oxidiertem LDL, sowie die Apoptose bei Schaumzellen.

Drittmittelgeber:

Deutsche Forschungsgemeinschaft

Beteiligte Wissenschaftler:

PD Dr. Paul Cullen, Dr. Manfred Fobker, Dr. Beate Brennhausen, Stefan Lorkowski, Claudia Wenner, Hildegard Hünting, Walburga Hanekamp, Karin Tegelkamp, Roland Schmidt

Veröffentlichungen:

Bhattacharya, S., D. Ameis, P. Cullen, T.M.E. Narcisi, J. Bayliss, C.P. Volpe: VNTR polymorphism in the hepatic lipase gene. Nucleic Acids Research 1991; 19:5088

Wojciechowski, A., M. Farrall, P. Cullen, T.M.E. Wilson, J.D. Bayliss, B. Farren, B.A. Griffin , M.J. Caslake, C.J. Packard, J. Shepherd, R. Thakker, J. Scott: Familial combined hyperlipidaemia linked to the apolipoprotein AI-CIII-AIV gene cluster on chromosome 11q23-q24. Nature 1991; 349:161-164.

Venkatesan, S., P. Cullen, P. Pacy, D. Halliday, J. Scott: Stable isotopes show a direct relation between VLDL apoB overproduction and serum triglyceride levels and indicate a metabolically and biochemically coherent basis for familial combined hyperlipidemia. Arteriosclerosis and Thrombosis 1993; 13:1110-1118.

Cullen, P., C.S. Rodgers, D. Callen, V.M. Connolly, P. Fells, H. Gordon, R.M. Winter, R.V. Thakker: Association of familial Duane syndrome and urogenital abnormalities with a bisatellited marker from chromosome 22. American Journal of Medical Genetics 1993; 47:925-930.

Shoulders, C.C., D.J. Brett, J.D. Bayliss, M.E. Narcisi, A. Jarmuz, T.T. Grantham, P.R.D. Leoni , S. Bhattacharya, P.M. Cullen, S. Levi, P.G.H. Byfield, P. Purkiss, J. Scott: Abetalipoproteinemia is caused by defects of the 97kDa subunit of a microsomal triglyceride transfer protein. Human Molecular Genetics 1993; 2:2109-2116. Abetalipoproteinemia is caused by defects of the 97kDa subunit of a microsomal triglyceride transfer protein. Human Molecular Genetics 1993; 2:2109-2116.

Cullen, P.: Genetics and Molecular Biology Editorial Comment. Current Opinion in Lipidology 1993; 4:V5-V6.

Cullen, P.: Genetics and Molecular Biology Editorial Comment. Current Opinion in Lipidology 1994; 5:U36-U37.

Graham, I., K. Robinson, G. Tomkin, N.C. Bradford, P. Wilkinson, B. Buckley, M. Seed, C.B. Marenah, J. Silas, N. Caplice, W. Fennell, Kaleem, J. Went, J. Repper, M. Vannan, D. Taylor, P.J. Richardson, Rittoo, A. Grant, T.B. Counihan, A.D. Hersh, S. Guptha, R. Gentry, J. Young, D.J. Gwilt, K. Fox, D. Mulcahy, R.H. Greenwood, D.B. Rowlands, R. Cramb, Arnsten, A.J. Mourant, Roberts, Santry, W.H. Taylor, B.A. Walker, S. Allen, D.A. Wood, S.A. Iversen, M.F. Laker, R.M. Gama, E.A. Hughes, A. Polanska, E.D. Bennett, Farrell, R. Wray, S. Ginks, P.A. Crean, M. Hall, Hartley: A one-year multicenter study of simvastatin in the treatment of hypercholesterolemia. British Journal Of Clinical Practice 1994; 48:231-235.

Cullen, P., B. Farren, J. Scott, M. Farrall: Complex segregation analysis provides evidence for a major gene acting on serum triglyceride levels in 55 British families with familial combined hyperlipidemia. Arteriosclerosis and Thrombosis 1994; 14:1233-1249.

Wiebusch, H., P. Cullen, J.S. Owen, D. Collins, P.S. Sharp, H. Funke, G. Assmann: Deficiency of lecithin:cholesterol acyltransferase due to compound heterozygosity of two novel mutations (Gly33Arg and 30-bp ins) in the LCAT gene. Human Molecular Genetics 1994; 4:143-145.

Assmann, G., A. von Eckardstein, P. Cullen: The Dyslipidemias in Fernandes J., Sandbury JM, van den Berghe G. (Eds.) Inborn Metabolic Diseases, Springer Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong Barcelona Budapest (1995) p. 261-268.

Assmann, G., P. Cullen: Erkennung und Behandlung von Fettstoffwechselstörungen - Aktuelle Empfehlungen Deutsches Ärzteblatt Supplement zur Ausgabe 52, 1995

Owen, J., H. Wiebusch, P. Cullen, G. Watts, V. Lima, H. Funke, G. Assmann: Complete deficiency of plasma lecithin-cholesterol acyltransferase (LCAT) activity due to a novel homozygous mutation (Gly30Ser) in the LCAT gene. Human Mutation 1996; 8:79-82.

Assmann, G., P. Cullen, J. Heinrich, H. Schulte: Hemostatic variables in the prediction or coronary risk: results of the 8 year follow-up of healthy men in the Münster Heart Study (PROCAM). Israel Journal of Medical Science 1996; 32:364-370.

Cullen, P., A. Cignarella, A. von Eckardstein, S. Mohr, G. Assmann: Phenotype-dependent differences in apolipoprotein E gene expression and protein secretion in human monocyte-derived macrophages. Circulation 1996; 94:1589.

Cullen, P., H. Schulte, G. Assmann: Umfassendes Risikokonzept. Münchener Medizinische Wochenschrift 1996; 138:447-450

Cullen, P., A. von Eckardstein, G. Assmann: Genetic and acquired abnormalities of lipoprotein metabolism. Cardiovascular Risk Factors 1996; 6: 99-121.

Assmann, G., P. Cullen, H. Schulte: HRT, plasma risk factors and cardiovascular disease. European Menopause Journal 1996; 3: 203-208

Mohr, S., P. Cullen, R. Schmidt, A. Cignarella, G. Assmann: Avoidance of false positives in PCR-based mRNA differential display during investigation of nonstandardized tissues or cells. Clinical Chemistry 1997; 43:182-184.

Berendes, E., M. Walter, P. Cullen, T. Prien, H. Van Aken, J. Horsthemke, M. Schulte, K. von Wild, R. Scherer: Brain natriuretic peptide and cerebral salt wasting in patients with aneurysmal subarachnoid haemorrhage. Lancet 1997; 349:245-249.

Cullen, P., M. Fobker, K. Tegelkamp, K. Meyer, F. Kannenberg, A. Cignarella, A. Benninghoven, G. Assmann: An improved method for quantification of cholesterol and cholesteryl esters in human monocyte-derived macrophages by high performance liquid chromatography with identification of unassigned cholesteryl ester species by means of secondary ion mass spectrometry. Journal of Lipid Research 1997; 38:401-409.

Cullen, P., H. Schulte, G. Assmann: The Münster Heart Study (PROCAM) - Total mortality is increased at low total and LDL-cholesterol concentrations in smokers but not in nonsmokers. Circulation 1997; 96:2128-2136.

Cullen, P., S. Mohr, B. Brennhausen, A. Cignarella, G. Assmann: Down regulation of the selectin ligand-producing fucosyltransferases Fuc-TIV and Fuc-TVII during foam cell formation in monocyte-derived macrophages. Arteriosclerosis, Thrombosis and Vascular Biology 1997; 17:1591-1598.

Cullen, P., K. Tegelkamp, M. Fobker, F. Kannenberg, A. Cignarella, G. Assmann: Measuring cholesterol in macrophages: Comparison of high-performance liquid chromatography and gas-liquid chromatography with enzymatic fluorometry. Analytical Biochemistry 1997; 251:39-44.

Heidenreich, S., M. Schmidt, C. August, P. Cullen, A. Rademaekers, H.G. Pauels: Regulation of human monocyte apoptosis by the CD14 molecule. Journal of Immunology 1997; 159:3178-3188.

Assmann, G., P. Cullen, H. Schulte: The Münster Heart Study - results of follow-up at 8 years. European Heart Journal 1997; 19:A2-A11.

Cullen, P., G. Assmann: Treatment goals for low density lipoprotein cholesterol in the secondary prevention of coronary heart disease: absolute levels or extent of lowering? American Journal of Cardiology 1997; 80:1287-1294.

Cullen, P.: Genetics and Molecular Biology Editorial Comment. Current Opinion in Lipidology 1997; 8: U33-U35

Assmann, G., H. Schulte, P. Cullen: New and classical risk factors- The Münster Heart Study (PROCAM). European Journal of Medical Research 1997; 2:237-242

Assmann, G., P. Cullen, H. Schulte: Managing global risk: new therapeutic objectives. Atherosclerosis 1997; 130:82.

Berendes, E., M. Walter, P. Cullen, H. van Aken, Th. Prien, K. von Wild, R. Scherer: Brain Natriuretic Peptide als Ursache des "Cerebral Salt Wasting" Syndroms. Anästhesiol. Intensivmed. Notfallmed Schmerztherapie 1997; 32:118.

Cullen, P., S. Mohr, G. Assmann: PCR-based mRNA Differential Display: Current Uses and Future Applications. European Journal of Clinical Chemistry and Clinical Biochemistry 1997; 35:A38.

Assmann, G., P. Cullen, H. Funke: Candidate genes in atherosclerosis. European Journal of Clinical Chemistry and Clinical Biochemistry 1997; 35:A16

Langer, C., P. Cullen, G. Assmann, A. von Eckardstein: Role of endogenous apo E in the regulation of cholesterol efflux from mouse peritoneal macrophages. European Journal of Clinical Chemistry and Clinical Biochemistry 1997; 35:A47.

Assmann, G., P. Cullen, A. von Eckardstein, H. Funke: Genetic dissection of high density lipoprotein metabolism. Atherosclerosis 1997; 134:5.

Cullen, P., A. Cignarella, B. Brennhausen, S. Mohr: Phenotype-dependent differences in apoE metabolism and cholesterol metabolism in human monocyte-derived macrophages. Atherosclerosis 1997; 134:229.

von Eckardstein, A., C. Langer, B. Wiesenhütter, P. Cullen, G. Assmann: Regulation of cholesterol efflux from mouse peritoneal macrophages by endogenous ApoE. Atherosclerosis 1997; 134:380.

von Eckardstein, A., P. Cullen, A. Cignarella, Y. Zhu, U. Daum, C. Langer, B. Wiesenhütter, G. Assmann: High density lipoprotein and reverse cholesterol transport. Lessons from natural mutations. Atherosclerosis 1997; 130:34.

Cullen, P., A. Cignarella, B. Brennhausen, A. von Eckardstein, G. Assmann: Differential effects of lovastatin on the trafficking of cellular and lipoprotein-derived cholesterol in human macrophages. Circulation 1997; 96:I-487.

Cullen, P., H. Funke, H. Schulte, G. Assmann: Lipoproteins and cardiovascular risk - from genetics to CHD prevention. Journal of Atherosclerosis and Thrombosis (Japan) 1997; 4: 1-8

Cullen, P., A. Cignarella, B. Brennhausen, A. von Eckardstein, S. Mohr, G. Assmann: Phenotype-dependent differences in apoE metabolism and in cholesterol homeostasis in human monocyte-derived macrophages. Journal of Clinical Investigation 1998; 101:1670-1677.

Cignarella, A., B. Brennhausen, A. von Eckardstein, G. Assmann, P. Cullen: Differential effects of lovastatin on the trafficking of endogenous and lipoprotein-derived cholesterol in human monocyte-derived macrophages, Arteriosclerosis, Thrombosis and Vascular Biology 1998; 18:1322-1329.

Rust, S., M. Walter, H. Funke, A. von Eckardstein, P. Cullen, H.Y. Kroes, R. Hordijk, J. Geisel, J. Kastelein, H.O.F. Molhuizen, M. Schreiner, A. Mischke, H.W. Hahmann, G. Assmann: Assignment of Tangier disease to chromosome 9q31 by a graphical linkage exclusion strategy Nature Genetics 1998; 20:96-98.

Assmann, G., R. Carmena, P. Cullen, J.-C. Fruchart, B. Lewis, M. Manicini, A. Olsson, R. Paoletti, M. Tikkanen, for the International Task Force for Prevention of Coronary Heart Disease: Coronary heart disease: reducing the risk. The scientific background to primary and secondary prevention of coronary heart disease - a worldwide view. Nutrition Metabolism and Cardiovascular Disease 1998; 8:158-217.

Cullen, P., H. Schulte, G. Assmann: Smoking, lipoproteins and coronary heart disease risk: data from the Münster Heart Study (PROCAM). European Heart Journal 1998; 19:1632-1634.

Assmann, G., P. Cullen, H. Schulte: Comment on the West of Scotland Study. Circulation 1998; 97:2033-2034.

Cullen, P., H. Funke, H. Schulte, G. Assmann: Lipoproteins and cardiovascular risk - from genetics to CHD prevention. European Heart Journal 1998; 19: C5-C11

Cullen, P.: Genetics and Molecular Biology Editorial Comment. Current Opinion in Lipidology 1998; 9:271-273

Cullen, P., G. Assmann: Current goals for low-density lipoprotein cholesterol. Cardiology Review 1998; 15:12-16

Cullen, P., G. Assmann: Diagnosis and management of new cardiovascular risk factors. European Heart Journal 1998; 19:O13-O19.

Cullen, P., A. Cignarella, G. Assmann: Apolipoprotein E und Cholesterinstoffwechsel humaner Makrophagen. Deutsche Gesellschaft für Klinische Chemie Mitteilungen 1998; 29:38-39.

Cullen, P., A. Cignarella, B. Brennhausen, G. Assmann: Effect of atorvastatin, the ACAT inhibitor CI-1011, and progesterone on storage and secretion of cholesterol in human monocyte-derived macrophages. Circulation 1998; 17:SS-2828.

Assmann, G., A. von Eckardstein, M. Walter, P. Cullen: Genetic dissection of high-density lipoprotein metabolism and reverse cholesterol transport. Jacotot B, Mathé D, Fruchart J.-C. (Eds.) Atherosclerosis XI. Proceedings of the XIth International Symposium on Atherosclerosis, Elsevier Science B.V. (1998) p. 19-28.

Cullen, P., H. Funke, H. Schulte, G. Assmann: Lipoproteins and cardiovascular risk: from genetics to prevention of coronary heart disease in Gotto AM, Lenfant C, Paoletti R, Catapano AL, Jackson AS (eds.) Multiple Risk Factors in Cardiovascular Disease - Strategies of Prevention of Coronary Heart Disease, Cardiac Failure and Stroke. Kluwer Academic Publishers, Dordrecht, Boston, London (1998), p. 217-228.

Cullen, P., J. Söffker, M. Höpfl, C. Bremer, R. Schlaghecken, T. Mehrens, F.K. Matzkies, G. Assmann, R.M. Schaefer: Hypochromic red cells and reticulocyte hemoglobin content in hemodialysis patients on erythropoietin. Nephrology, Dialysis and Transplantation 1999; 14:659-665.

Schulte, H., P. Cullen, G. Assmann: Obesity, mortality and cardiovascular disease in the Münster Heart Study (PROCAM). Atherosclerosis 1999; 144:199-209

Assmann, G., P. Cullen, A. von Eckardstein, H. Funke, H. Schulte: The importance of triglycerides as a significant risk factor. European Heart Journal 1999 1: J7-J11

Daum, U., T.P. Leren, C. Langer, A. Chirazi, P. Cullen, P.H. Pritchard, G. Assmann, A. von Eckardstein: Multiple dysfunctions of two apolipoprotein A-I (ApoA-I) variants, apoA-I(R160L)Oslo and ApoA-I(P165R), which are associated with hypo-alphalipoproteinemia in heterozygous carriers. Journal of Lipid Research 1999; 40: 486-494

Assmann, G., P. Cullen, R. Carmena, J.-C. Fruchart, B. Lewis, M. Mancini: Re: Recommendations of the 2nd Joint Task Force of the European Societies of Atherosclerosis, Cardiology and Hypertension. European Heart Journal 1999; 20: 841-843.

Weitkamp, B.*, P.* Cullen, G. Plenz, H. Robenek, J. Rauterberg: Human macrophages synthesize type VIII collagen in vitro and in the atherosclerotic plaque. FASEB Journal 1999; 13:1445-1457 (*geteilte Erstautorenschaft).

Assmann, G., P. Cullen, F. Jossa, B. Lewis, M. Mancini, for the International Task Force for Prevention of Coronary Heart Disease: Coronary heart disease: reducing the risk. The scientific basis to primary and secondary prevention of coronary heart disease. Arteriosclerosis, Thrombosis, and Vascular Biology 1999; 19:1819-1824.

Erren, M., H. Reinecke, J.O. Schurek, J. Kropf, M. Fobker, R. Junker, S. Kerber, G. Breithardt, G. Assmann, P. Cullen: Inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries. Arteriosclerosis, Thrombosis and Vascular Biology 1999; 19:2355-2363.

Assmann, G., R. Carmena, P. Cullen, J.-C. Fruchart, F. Jossa, B. Lewis, M. Mancini, R. Paoletti: Coronary heart disease - reducing the risk, a worldwide view. Clinical Recommendations 1998. Circulation 1999; 100: 1930-1938

Schulte, H., P. Cullen, G. Assmann: Update kardiovaskulärer Risikofaktoren - die PROCAM-Studie. Berliner Ärzte 5/99: 1-33

Cullen, P., H. Schulte, U. Wahrburg, G. Assmann: Neue Methoden zur Identifizierung von koronaren Hochrisikopatienten in der täglichen Praxis. Ärztliche Praxis 16. Juni 1999, S. 42.

Cullen, P.: Reply to letter by Grainger et al. Risk factors in atheroscerlosis. Journal of the Irish College of Physicians and Surgeons 1999; 28:175-176.

Cullen, P., G. Assmann: High risk strategies for atherosclerosis. Clinica Chimica Acta 1999; 286:31-45.

Cullen, P., A. von Eckardstein, G. Assmann: Dyslipidemia and cardiovascular risk in diabetes. Diabetes Obesity and Metabolism 1999; 1: 189-198.

Assmann, G., A.M. Gotto Jr., P. Cullen: Treatement of elevated low density lipoprotein cholesterol - the role of LDL apheresis. Medical Science Publications Inc., Osaka, Japan, 1999. ISBN 4-900657-72-7 C3047 P3000E

Assmann, G., A. von Eckardstein, H. Funke, P. Cullen, M. Walter, H. Schulte: The protective effect of HDL in atherosclerosis. Atherosclerosis 1999; 144: 3-4.

von Eckardstein, A., C. Langer, P. Cullen, G. Assmann: Regulation of cellular lipid metabolism in macrophages by endogenous apoE and exogenous HDL and lipid-free lipoproteins. Atherosclerosis 1999; 144: 5.

Cignarella, A., B. Brennhausen, A. Puglisi, A. von Eckardstein, G. Assmann, P. Cullen: Lovastatin modulates intracellular cholesterol transport in human monocyte-derived macrophages. Atherosclerosis 1999; 144: 41.

Kratz, M., P. Cullen, A. Kassner, M. Fobker, P.M. Abuja, H. Schulte, G. Assmann, U. Wahrburg: The impact of dietary fatty acids on susceptibility of low-density lipoprotein to oxidation. Atherosclerosis 1999; 144: 129.

Cignarella, A., B. Brennhausen, L. Puglisi, A. von Eckardstein, G. Assmann, P. Cullen: The common apoE polymorphism affects apoE metabolism and cholesterol homeostasis in human monocyte-derived macrophages. Atherosclerosis 1999: 145: S6

Cullen, P., H. Schulte, G. Assmann: Triglycerides as an independent coronary heart disease risk factor: controversy and new evidence. American Journal of Cardiology (in Druck)

Cullen, P.: Triglycerides - a forgotten risk factor. Journal of the Irish College of Physicians and Surgeons (in Druck)

Matzkies, F.K., P. Cullen, L. Schaefer, M. Hartmann, R.M. Schaefer: Zinc protopoporphyrin and percentage of hypochromic erythrocytes as markers of functional iron deficiency during therapy with erythropoietin in patients with advanced AIDS. Southern Medical Journal (in Druck).