Petar Alaupovic

Abstract

HomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 34, No. 6Petar Alaupovic Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBPetar AlaupovicThe Father of Lipoprotein Classification Based on Apolipoprotein Composition Frank M. Sacks and H. Bryan Brewer Frank M. SacksFrank M. Sacks From the Department of Nutrition, Harvard School of Public Health, Boston, MA. (F.M.S.); and the Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, DC (H.B.B.) Search for more papers by this author and H. Bryan BrewerH. Bryan Brewer From the Department of Nutrition, Harvard School of Public Health, Boston, MA. (F.M.S.); and the Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, DC (H.B.B.) Search for more papers by this author Originally published1 Jun 2014https://doi.org/10.1161/ATVBAHA.114.303500Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;34:1111–1113IntroductionPetar Alaupovic, an internationally renowned biochemist and lipidologist, died on January 30, 2014, in Oklahoma City at the age of 91 years. Dr Alaupovic was a founder of the modern field of lipoproteins whose ideas continue to have an impact on its development. He performed research and taught at Oklahoma Medical Research Foundation since 1960.In 1964, Dr Alaupovic, known to his colleagues as Dr A or Pierre, proposed a revolutionary new classification system for lipoproteins. Until that time, the classification of lipoproteins focused on the physical properties of lipoproteins, emphasizing the lipid component and the size of the lipoprotein particle. However, Dr Alaupovic considered the protein part to have great biological importance that directed every step in the metabolism of lipoproteins and determined their effects on atherosclerosis. When he began his research on lipoproteins, there were considered to be just 2 apolipoproteins, apolipoprotein B and apolipoprotein A. Using immunologic and protein chemistry techniques, he isolated and characterized several additional apolipoproteins associated with lipoproteins. He proposed the ABC nomenclature for apolipoproteins, which initially included apolipoproteins A-I, A-II, B, C-I, C-II, C-III, D, and E. Most important to the subsequent progress in the field of lipoprotein, he subdivided the major lipoprotein classes, apolipoprotein A-I and apolipoprotein B lipoproteins, according to their content of other apolipoproteins that, although not required for their formation and secretion, confer specific crucial functions to lipoproteins. Thus, a second major change in his classification system from the prevailing view of lipoproteins at that time was the concept that there were separate and distinct lipoprotein particles or families with defined apolipoprotein composition within the major density classes of very-low-density, intermediate-density, low-density, and high-density lipoproteins. Dr Alaupovic hypothesized that apolipoprotein E and the apolipoprotein Cs are not randomly scattered among all the apolipoprotein B and apolipoprotein A-I lipoproteins but are focused on specific subfractions that comprise a percentage of the total. He divided apolipoprotein B into lipoprotein B:E (containing apolipoproteins B and E), lipoprotein B:C-III (containing apolipoproteins B and C-III), lipoprotein B:E:CIII (containing apolipoproteins B, E, and C-III), and lipoprotein B (containing apolipoproteins B, but not apolipoprotein E or C-III). Dr Alaupovic showed that these lipoprotein subtypes have specific functions and relation to atherosclerosis. Thus, Dr Alaupovic conceived the concept and demonstrated the biological and clinical importance of lipoprotein speciation.These radical changes in the concepts of the heterogeneity of plasma apolipoproteins and lipoproteins and the need for the development of a new classification system for lipoprotein particles were only slowly accepted. Despite initial resistance to Dr Alaupovic's new concepts of apolipoproteins and lipoprotein particles or families, he persevered and the lipoprotein field has gradually understood the classification system for apolipoproteins and lipoprotein particles, and his review in Methods in Enzymology 30 is a classic in the lipoprotein field. His classification system has become adopted by scientists and clinicians around the globe. Dr Alaupovic’s legacy extends to a growing number of research groups that are building on his work by studying intensively the action of apolipoproteins and the basis for speciation of apolipoprotein B and apolipoprotein A-I lipoproteins.Petar Alaupovic was born August 3, 1923, in Prague, Czechoslovaskia. He and his family of 2 brothers moved to Zagreb, Croatia, where he attended elementary and high school under the tutelage of his grandfather, Tugomir Alaupovic, an accomplished poet and politician. In addition to pursuing his studies, he was an accomplished athlete in soccer, water polo, and cross-country skiing. In 1947, Alaupovic married his beloved Alexandra, who later became an internationally known artist. He and Alexandra were together for 65 years until her death on January 2, 2013. Betsy, their only child, was born in 1949. In 1956, Alaupovic received his PhD in Chemistry at the University of Zagreb. In 1957, Dr Alaupovic accepted a research fellowship at the University of Illinois, and he immigrated with his wife and daughter to the United States. In 1960, Dr Alaupovic accepted a position in the Cardiovascular Section at Oklahoma Medical Research Foundation. In 1964, Dr Alaupovic and his family became US citizens. Dr Alaupovic’s contributions to the field of lipoproteins will remain as a model for young scientists to understand the challenges and persistence that are required to advance science. During his 53-year career at Oklahoma Medical Research Foundation, Dr Alaupovic remained passionate about the importance of apolipoproteins and lipoprotein particles in the development of cardiovascular disease and as a target to reduce heart disease. Although he retired at the age of 88, he continued to go to his office each day to work on articles and reviews. Throughout his career, and especially in his later years, Dr Alaupovic extended the application of lipoprotein particle types to gain insight on diseases other than cardiovascular disease. Remarkably, his bibliography includes 9 research publications in 2013. Dr Alaupovic was appreciated by all for his warmth, kindness, and complete sincerity.Dr Alaupovic was a frequent lecturer throughout the world and received numerous awards and honorary degrees during his career. He published >330 scientific papers. During his career, he supervised >20 PhD candidates and 72 postdoctoral fellows. Numerous current experts in lipoproteins and atherosclerosis had the privilege of spending time during their career in Oklahoma City with a memory of excellent science and unforgettable wine-testing with Pierre and Alexandra as the consummate hosts. Dr Alaupovic received numerous awards including the prestigious Distinguished Career Scientist Award from the Oklahoma Medical Research Foundation; honorary doctoral degree from the University of Lille, France; honorary diploma from the National University of La Plata, Argentina; honorary doctoral degree from the University of Buenos Aires, Argentina; honorary doctoral degree from the University of Goteborg, Sweden; and Special Recognition Award from the Council on Arteriosclerosis, American Heart Association. Dr Alaupovic had a remarkable scientific career during which he not only established a new paradigm, lipoprotein classification based on apolipoprotein composition, but also directly touched the careers and lives of innumerable trainees and colleagues. Dr Alaupovic is survived by his daughter Betsy Alaupovic Hyde in the Oklahoma City and 2 grandsons: Homer Clark Hyde and his wife Aga in Chicago, and Robert Alexander Hyde and his wife Mary in Cleveland, OH.DisclosuresNone.FootnotesCorrespondence to Frank M. Sacks, MD, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail [email protected]Select Publications From a Total of 255 Listed in PubMed1. Gustafson A, Alaupovic P, Furman RH. Studies of the composition and structure of serum lipoproteins: physical-chemical characterization of phospholipid-protein residues obtained from very-low-density human serum lipoproteins.Biochim Biophys Acta. 1964; 84:767–769.MedlineGoogle Scholar2. Gustafson A, Alaupovic P, Furman RH. Studies of the composition and structure of serum lipoproteins: isolation, purification, and characterization of very low density lipoproteins of human serum.Biochemistry. 1965; 4:596–605.CrossrefMedlineGoogle Scholar3. Seidel D, Alaupovic P, Furman RH. A lipoprotein characterizing obstructive jaundice. I. Method for quantitative separation and identification of lipoproteins in jaundiced subjects.J Clin Invest. 1969; 48:1211–1223.CrossrefMedlineGoogle Scholar4. Ganesan D, Bradford RH, Alaupovic P, McConathy WJ. Differential activation of lipoprotein lipase from human post-heparin plasma, milk and adipose tissue by polypeptides of human serum apolipoprotein C.FEBS Lett. 1971; 15:205–208.CrossrefMedlineGoogle Scholar5. Kostner G, Alaupovic P. Studies of the composition and structure of plasma lipoproteins. Separation and quantification of the lipoprotein families occurring in the high density lipoproteins of human plasma.Biochemistry. 1972; 11:3419–3428.CrossrefMedlineGoogle Scholar6. McConathy WJ, Alaupovic P. Isolation and partial characterization of apolipoprotein D: a new protein moiety of the human plasma lipoprotein system.FEBS Lett. 1973; 37:178–182.CrossrefMedlineGoogle Scholar7. Lee DM, Alaupović P. Composition and concentration of apolipoproteins in very-low-and low-density lipoproteins of normal human plasma.Atherosclerosis. 1974; 19:501–520.MedlineGoogle Scholar8. Alaupovic P, McConathy WJ, Curry MD, Magnani HN, Torsvik H, Berg K, Gjone E. Apolipoproteins and lipoprotein families in familial lecithin: cholesterol acyltransferase deficiency.Scand J Clin Lab Invest Suppl. 1974; 137:83–87.CrossrefMedlineGoogle Scholar9. Campbell DP, Poley JR, Alaupovic P. Determination of serum lipoprotein-X for the early differentiation between neonatal hepatitis and biliary atresia.J Surg Res. 1975; 18:385–390.CrossrefMedlineGoogle Scholar10. Kelly JL, Alaupovic P. Lipid transport in the avian species. Part 2. Isolation and characterization of lipoprotein A and lipoprotein B, two major lipoprotein families of the male turkey serum lipoprotein system.Atherosclerosis. 1976; 24:177–187.CrossrefMedlineGoogle Scholar11. Olofsson SO, McConathy WJ, Alaupovic P. Isolation and partial characterization of a new acidic apolipoprotein (apolipoprotein F) from high density lipoproteins of human plasma.Biochemistry. 1978; 17:1032–1036.CrossrefMedlineGoogle Scholar12. Suenram A, McConathy WJ, Alaupovic P. Evidence for the lipoprotein heterogeneity of human plasma high density lipoproteins isolated by three different procedures.Lipids. 1979; 14:505–510.CrossrefMedlineGoogle Scholar13. Illingworth DR, Connor WE, Alaupovic P. High density lipoprotein metabolism in a patient with abetalipoproteninemia.Ann Nutr Metab. 1981; 25:1–10.CrossrefMedlineGoogle Scholar14. Alaupovic P, Schaefer EJ, McConathy WJ, Fesmire JD, Brewer HBPlasma apolipoprotein concentrations in familial apolipoprotein A-I and A-II deficiency (Tangier disease).Metabolism. 1981; 30:805–809.CrossrefMedlineGoogle Scholar15. Norum RA, Lakier JB, Goldstein S, Angel A, Goldberg RB, Block WD, Noffze DK, Dolphin PJ, Edelglass J, Bogorad DD, Alaupovic P. Familial deficiency of apolipoproteins A-I and C-III and precocious coronary-artery disease.N Engl J Med. 1982; 306:1513–1519.CrossrefMedlineGoogle Scholar16. Breckenridge WC, Alaupovic P, Cox DW, Little JA. Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency.Atherosclerosis. 1982; 44:223–235.CrossrefMedlineGoogle Scholar17. Koren E, McConathy WJ, Alaupovic P. Isolation and characterization of simple and complex lipoproteins containing apolipoprotein F from human plasma.Biochemistry. 1982; 21:5347–5351.CrossrefMedlineGoogle Scholar18. Milne RW, Weech PK, Blanchette L, Davignon J, Alaupovic P, Marcel YL. Isolation and characterization of apolipoprotein B-48 and B-100 very low density lipoproteins from type III hyperlipoproteinemic subjects.J Clin Invest. 1984; 73:816–823.CrossrefMedlineGoogle Scholar19. Lee DM, Alaupovic P. Apolipoproteins B, C-III and E in two major subpopulations of low-density lipoproteins.Biochim Biophys Acta. 1986; 879:126–133.CrossrefMedlineGoogle Scholar20. Dashti N, Alaupovic P, Knight-Gibson C, Koren E. Identification and partial characterization of discrete apolipoprotein B containing lipoprotein particles produced by human hepatoma cell line HepG2.Biochemistry. 1987; 26:4837–4846.CrossrefMedlineGoogle Scholar21. Attman PO, Alaupovic P, Gustafson A. Serum apolipoprotein profile of patients with chronic renal failure.Kidney Int. 1987; 32:368–375.CrossrefMedlineGoogle Scholar22. Dashti N, Koren E, Alaupovic P. Identification and partial characterization of discrete apolipoprotein A-containing lipoprotein particles secreted by human hepatoma cell line HepG2.Biochem Biophys Res Commun. 1989; 163:574–580.CrossrefMedlineGoogle Scholar23. Blankenhorn DH, Alaupovic P, Wickham E, Chin HP, Azen SP. Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Lipid and nonlipid factors.Circulation. 1990; 81:470–476.LinkGoogle Scholar24. Alaupovic P. Apolipoprotein composition as the basis for classifying plasma lipoproteins. Characterization of ApoA- and ApoB-containing lipoprotein families.Prog Lipid Res. 1991; 30:105–138.CrossrefMedlineGoogle Scholar25. Alaupovic P, Knight-Gibson C, Wang CS, Downs D, Koren E, Brewer HB, Gregg RE. Isolation and characterization of an apoA-II-containing lipoprotein (LP-A-II:B complex) from plasma very low density lipoproteins of patients with Tangier disease and type V hyperlipoproteinemia.J Lipid Res. 1991; 32:9–19.CrossrefMedlineGoogle Scholar26. Alaupovic P, Bard JM, Tavella M, Shafer D. Identification of apoB-containing lipoprotein families in NIDDM.Diabetes. 1992; 41(suppl 2):18–25.CrossrefMedlineGoogle Scholar27. Bekaert ED, Alaupovic P, Knight-Gibson CS, Franceschini G, Sirtori CR. Apolipoprotein A-I Milano: sex-related differences in the concentration and composition of apoA-I- and apoB-containing lipoprotein particles.J Lipid Res. 1993; 34:111–123.CrossrefMedlineGoogle Scholar28. Hodis HN, Mack WJ, Azen SP, Alaupovic P, Pogoda JM, LaBree L, Hemphill LC, Kramsch DM, Blankenhorn DH. Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin.Circulation. 1994; 90:42–49.LinkGoogle Scholar29. Alaupovic P, Hodis HN, Knight-Gibson C, Mack WJ, LaBree L, Cashin-Hemphill L, Corder CN, Kramsch DM, Blankenhorn DH. Effects of lovastatin on ApoA- and ApoB-containing lipoproteins. Families in a subpopulation of patients participating in the Monitored Atherosclerosis Regression Study (MARS).Arterioscler Thromb. 1994; 14:1906–1913.LinkGoogle Scholar30. Alaupovic P. Significance of apolipoproteins for structure, function, and classification of plasma lipoproteins.Methods Enzymol. 1996; 263:32–60.CrossrefMedlineGoogle Scholar31. Koren E, Corder C, Mueller G, Centurion H, Hallum G, Fesmire J, McConathy WD, Alaupovic P. Triglyceride enriched lipoprotein particles correlate with the severity of coronary artery disease.Atherosclerosis. 1996; 122:105–115.CrossrefMedlineGoogle Scholar32. Alaupovic P, Mack WJ, Knight-Gibson C, Hodis HN. The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial.Arterioscler Thromb Vasc Biol. 1997; 17:715–722.LinkGoogle Scholar33. Samuelsson O, Attman PO, Knight-Gibson C, Larsson R, Mulec H, Weiss L, Alaupovic P. Complex apolipoprotein B-containing lipoprotein particles are associated with a higher rate of progression of human chronic renal insufficiency.J Am Soc Nephrol. 1998; 9:1482–1488.CrossrefMedlineGoogle Scholar34. Sacks FM, Alaupovic P, Moye LA, Cole TG, Sussex B, Stampfer MJ, Pfeffer MA, Braunwald E. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial.Circulation. 2000; 102:1886–1892.LinkGoogle Scholar35. Schweitzer M, Tessier D, Vlahos WD, Leiter L, Collet JP, McQueen MJ, Harvey L, Alaupovic P. A comparison of pravastatin and gemfibrozil in the treatment of dyslipoproteinemia in patients with non-insulin-dependent diabetes mellitus.Atherosclerosis. 2002; 162:201–210.CrossrefMedlineGoogle Scholar36. Sacks FM, Alaupovic P, Moye LA. Effect of pravastatin on apolipoproteins B and C-III in very-low-density lipoproteins and low-density lipoproteins.Am J Cardiol. 2002; 90:165–167.CrossrefMedlineGoogle Scholar37. Hannuksela ML, Brousseau ME, Meyn SM, Nazih H, Bader G, Shamburek RD, Alaupovic P, Brewer HBIn vivo metabolism of apolipoprotein E within the HDL subpopulations LpE, LpE:A-I, LpE:A-II and LpE:A-I:A-II.Atherosclerosis. 2002; 165:205–220.CrossrefMedlineGoogle Scholar38. Blackett PR, Blevins KS, Quintana E, Stoddart M, Wang W, Alaupovic P, Lee ET. ApoC-III bound to apoB-containing lipoproteins increase with insulin resistance in Cherokee Indian youth.Metabolism. 2005; 54:180–187.CrossrefMedlineGoogle Scholar39. Hilpert KF, West SG, Kris-Etherton PM, Hecker KD, Simpson NM, Alaupovic P. Postprandial effect of n-3 polyunsaturated fatty acids on apolipoprotein B-containing lipoproteins and vascular reactivity in type 2 diabetes.Am J Clin Nutr. 2007; 85:369–376.CrossrefMedlineGoogle Scholar40. Lee DM, Alaupovic P, Knight-Gibson C, Bagdade JD. Apolipoprotein-B subclasses as acceptors of cholesteryl esters transferred by CETP.Eur J Clin Invest. 2008; 38:734–742.CrossrefMedlineGoogle Scholar41. Sacks FM, Rudel LL, Conner A, Akeefe H, Kostner G, Baki T, Rothblat G, de la Llera-Moya M, Asztalos B, Perlman T, Zheng C, Alaupovic P, Maltais JA, Brewer HB. Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo.J Lipid Res. 2009; 50:894–907.CrossrefMedlineGoogle Scholar42. Bagdade J, Pedersen BK, Schwenke D, Saremi A, Alaupovic P. Acute effects of interleukin-6 infusion on apo-B-containing lipoprotein subclasses in humans.Scand J Clin Lab Invest. 2011; 71:449–455.CrossrefMedlineGoogle Scholar43. Knowlton N, Wages JA, Centola MB, Alaupovic P. Apolipoprotein-defined lipoprotein abnormalities in rheumatoid arthritis patients and their potential impact on cardiovascular disease.Scand J Rheumatol. 2012; 41:165–169.CrossrefMedlineGoogle Scholar44. Wang W, Khan S, Blackett P, Alaupovic P, Lee E. Apolipoproteins A-I, B, and C-III in young adult Cherokee with metabolic syndrome with or without type 2 diabetes.J Clin Lipidol. 2013; 7:38–42.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByFurtado J, Yamamoto R, Melchior J, Andraski A, Gamez-Guerrero M, Mulcahy P, He Z, Cai T, Davidson W and Sacks F (2018) Distinct Proteomic Signatures in 16 HDL (High-Density Lipoprotein) Subspecies, Arteriosclerosis, Thrombosis, and Vascular Biology, 38:12, (2827-2842), Online publication date: 1-Dec-2018. Singh S, Miyosawa K and Aikawa M (2015) Mass spectrometry meets the challenge of understanding the complexity of the lipoproteome: recent findings regarding proteins involved in dyslipidemia and cardiovascular disease, Expert Review of Proteomics, 10.1586/14789450.2015.1078731, 12:5, (519-532), Online publication date: 3-Sep-2015. Sacks F (2015) The crucial roles of apolipoproteins E and C-III in apoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia, Current Opinion in Lipidology, 10.1097/MOL.0000000000000146, 26:1, (56-63), Online publication date: 1-Feb-2015. June 2014Vol 34, Issue 6 Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/ATVBAHA.114.303500PMID: 24945028 Originally publishedJune 1, 2014 PDF download Advertisement