Вариабельность концентрации липопротеина(а) и структурная организация генов аполипопротеина(а) и ингибитора активатора плазминогена 1 типа в норме и при инфаркте миокарда тема диссертации и автореферата по ВАК РФ 03.00.04, кандидат биологических наук Волкова, Мария Владимировна

• Волкова, Мария Владимировна
• кандидат биологических наук
• 2000

Оглавление диссертации кандидат биологических наук Волкова, Мария Владимировна

Список используемых сокращений.

Введение:

Актуальность проблемы.

Цели и задачи исследования.

Научная новизна полученных результатов.

Научно-практическая значимость работы.

Апробация работы.

Структура и объем диссертации.

Обзор литературы:

Липопротеин(а) . Структура и состав.

Структура гена апо(а).

Метаболизм.

Липопротеин(а) и клинические проявления атеросклероза.:.

Ингибитор активатора плазминогена 1 типа. Система фибринолиза и ингибитор активатора плазминогена типа.

Структура гена ИАПГ-1.

Метаболизм.

ИАПГ-1 и атеротромбоз.

Заключение диссертации по теме «Биохимия», Волкова, Мария Владимировна

112 ВЫВОДЫ:

1. В популяции Санкт-Петербурга уровень ЛП(а) находится под жестким генетическим контролем

2. В популяции Санкт-Петербурга изменчивость уровня ЛЩа) на 35% объясняется вариабельностью числа KIV-2 повторов.

3. В группе больных с ИМ в возрасте до 45 лет найдена обратная корреляция между числом пентануклеотидных повторов в промоторной области гена аполипопротеина(а) и уровнем ЛП(а). Этот эффект не зависит от вариабельности числа KIV-2 повторов гена аполипопротеина(а).

4. В популяции г.Санкт-Петербурга повышенный уровень ЛЩа) и число KIV-2 повторов меньше 2 0 в гене апо(а) являются факторами риска развития ИМ в возрасте до 45 лет.

5. Аллель 4G инсерционно-делеционного полиморфизма в позиции -675 гена ИАПГ-1 достоверно чаще встречается в группе пациентов, с момента ИМ которых прошло более б месяцев и достоверно реже среди больных острого периода ИМ.

Список литературы диссертационного исследования кандидат биологических наук Волкова, Мария Владимировна, 2000 год

1. М.В. Ежов, О.И. Афанасьева, Г.Ф. Беневоленская, А.П. Савченко, А. А. Лякишев. С.Н. Покровский. Связь фенотипа апобелка(а) с наличием ишемической болезни сердца у мужчин молодого возраста// Кардиология.-1999.-Т.39.-С.12-15.

2. Alessi M.C., Juhan-Vague I., Kooistra Т., Declerck P.J., Collen D. Insulin stimulates the synthesis of plasminogen activator Inhibitor 1 by the human hepatocellular cell line Hep G2// Thromb. Haemost.-1988.-V.60.-P.491-494.

3. Argraves K., Kozarsky -K. F., Fallon J.Т., Harpel P.C. and Strikland D.K. The atherogenic lipoprotein(a) is internalized and degraded in a process mediated by the VLDL receptor// J. Clin. Invest.-1997.-V.100.-P.2170-2181.

4. Armstrong V.W., Walli A.K. and Seidel P. Isolation, characterization and uptake in human fibroblasts of an apo(a)-free lipoprotein obtained in reduction of lipoprotein<a)// J. Lipid. Res.-1985.-V.26.-P.1314-1323.

5. Assmann G., Schulte H. and von Eckardstein A. Hypertriglyceridemia and elevated lipoprotein (a) are risk factors for major coronary events in middle-aged men/'/ Am. J. Cardiol.-1996.-V.77.-P.117 9-1184.

6. Austin M.A., Sandholzer C., Selby J.V., Newman В., Krauss R.M. and Utermann G. Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein phenotypes// Am. J. Hum. Genet.-1992.-V.51.-P.829-840.

7. Bachmann F., Juhan-Vague I. and Alessi M.C. Plasminogen activator inhibitor 1 and atherothrombosis// Thromb. Haemost.-1993.-V.70.-P.138-143.

8. Bard J-M., Delattre-Lestavel S., Clavey V. , Pont P., Derudas В., Parra H-J. and Fruchard J-C. Isolation and characterisation of two sub-species of Lp(a), one containing apo E and one free of Apo E// Biochem. Biophys. Acta.-1992.-V.1127.-P.124-130.

9. Boerwinkele E., Menzel H.J., Kraft H-G. and Utermann G. Genetics of the guantitative Lp(a) lipoprotein trait// Ниш. Genet.-1989.-V.82.-P.73-78.

10. Boerwinkle E., Leffert C.C., Lackner C. , Chiesa G., Hobbs H.H. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations// J. Clin. Invest.-1992.-V.90.-P.52-60.

11. Boomsma D.I., Kaptain A., Kempen H.J.M., Leuven J.A. and Princen H.M.G. Lipoprotein (a): relation to other risk factorsand genetic heritability. Results from a Ditch parent-twin study// Atherosclerosis.-1993.-V.99.-P.23-33.

12. Booth N.A., Simpson A.J., Croll A., Bennett В., MacGregor I.R. PAI-1 in plasma and platelets// Brit. J. Haematol.-1988.-V.70.-P.327-333.

13. Bosma P.J., van den Berg E.A. Kooistra T. Human PAI-1 gene// J. Biol. Chem.-1988.-V.263.-P.9129-9141.

14. Breslow J.L., Azrolan N. and Bostom A. N-acetylcysteine and lipoprotein(a)// Lancet.-1992.-V.339.-P.126-127.

15. Callow M.J., Stolzf us L.J., Lawn R.M. and Rubin E.M. Expression of human apolipoprotein В and assembly of lipoprotein(a) in transgenic mice// Proc. Natl. Acad. Sci.-1994.-V.91.-P.2130-2134.

16. Carmeliet P., Collen D. Molecular genetics of the fibrinolytic and coagulation systems in haemostasis, thrombogenesis, restenosis and atherosclerosis// Curr. Opin. Lipidol.-1997.-V.8.-P.118-125.

17. Cesari M., Sartori M.T., Patrassi G.M., Vettore S., Rossi G.P. Determinants of plasma levels of plasminogen activator inhibitor-1: a study of normotensive twins// Arterioscler. Thromb. Vase. Biol.-1999.-V.19.-P.316-320.

18. Cobbaert C. and Kesteroot H. Serum lipoprotein (a) levels in racially different populations// Am. J. Epidemiol.-1992.-V.136.-P. 441-449.

19. Collen D. and Lijnen HR. Basic and clinical aspects of fibrinolysis and thrombolysis// Blood.-1991.-V.78.-P.3114-3124.

20. Cox L.A., Jett C. and Hixson J.E. Molecular basis of arv apolipoprotein null allele: a splice mutation is associated with deletion of a single exon// J. Lipid. Res.-1998.-V.39.-P.1319-1326.

21. Dahlen G., Ericson C., Furberg C., Lundkvist L. and Svaerdsudd K. Studies on an extrapre-beta lipoprotein fraction// Acta. Med. Scand.-1972.-Suppl.531.-P.1-29.

22. Dichek D., Quertermous T. Thrombin regulation of mRNA levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in cultured human umbilical vein endothelial cells// Blood.-1989.-V.74.-P.222-228.

23. Doucet C., Huby Т., Chapman J. and Tillet J. Lipoprotein (a) in the chimpanzee: relationship of apo(a) phenotype to elevated plasma Lp<a) levels// J. Lipid. Res.-1994.-V.35.-P.263-270.

24. Drayana D.T., Hegele R.A., Haas P.E., Emi M., Wu L.L., Eaton D.L., Lawn R.M., Williams R.R., White R.L. and Lalouel J.M. Genetic linkage between lipoprotein(a) phenotype and a DNApolymorphism in the plasminogen gene// Genomics.-1988.-V.3.-P.230-236.

25. Durovic S., Marz W., Frank S. Decreased binding of apolipoprotein(a) to familial defective apolipoprotein B100 -(Arg3500Gln) // J. Biol. Chem.-1994 .-V. 269.-P. 30320-30325 .

26. Edelberg J.M. and Pizzo S.V. Lipoprotein (a) : the link between impaired fibrinolysis and atherosclerosis// Fibrinolysis.-1991.-V.5.-P.135-143.

27. Edelberg J.M., Reilly C.F., Pizzo S.V. The inhibition of tissue type plasminogen activator by plasminogen activator inhibitor-1. The effects of fibrinogen, heparin, vitronectin, and lipoprotein(a)// J. Biol. Chem.-1991.-V.266.-P.7488r7493 .

28. Edelberg J.M., Pizzo S.V. Lipoprotein {a) in the regulation of fibrinolysis// Atheroscler. Thromb.-1995.-V.2.-Suppl.1.-P.S5-7 .

29. Ehrlich K.C. and Ehrlich M. Highly repeated sites in the apolipoprotein(a) gene recognized by methylated DNA-binding protein, a sequence specific DNA-binding protein// Mol. Cell. Biol.-1990.-V.10.-P.4957-4960.

30. Emeis J.J., Kooistra T. Interleukin 1 and lipopolysaccharide induce an inhibitor of tissue-type plasminogen activator in vivo and in cultured endothelial cells// J. Exp. Med.-1986.-V.163.-P.1260-1266.

31. Eriksson P., Kallin В., van't Hooft F.M., Bavenhoim P., Hamsten A. Allele-specific increase in basal transcription of the plasminogen activator inhibitor-1 gene is associated with myocardial infarction// Proc. Natl. Acad. Sci.-1995.-V.92.-P.1851-1855.

32. Espeland M.A., Marcovina S.M., Miller V., Wood P.O., Wasilauskak C., Sherwin R. , Schrott H., Bush T.L. Effect of postmenopausal hormone therapy on lipoprotein(a) concentration// Circulation.-1998.-V.97.-P.979-986.

33. Feely J., Barry M., Keeling P.W.N., Weir D.G. and Cook T. Lipoprotein(a) in cirrhosis// BMJ.-1992.-V.304.-P.545-546.

34. Fless G.M., Pfaffinger D. and Scanu A.M. Relative affinity of human Lp-(a) , ApoB-100-Apo (a) and Apo (a) for various lipoproteins// Circulation.-1989.-V.80.-P.11-180.

35. Fless G.M., Pfaffinger 0., Eisenbart J.D. and Scanu A.M. Solubility, immunochemical and lipoprotein binding properties of apoB100-apo{a), the protein moiety of lipoprotein(a)// J. Lipid. Res.-1990.-V.31.-P.909-918.

36. Folio M. , Ginsburg D. Structure and expression "of the human gene encoding plasminogen activator inhibitor, PAI-1// Gene.-1989.-V.84.-P.447-453.

37. Frank S., Durovik S. and Kostner -G.M. The assembly of lipoprotein Lp(a)// Eur. J. Clin. Invest.-1996.-V.26.-P.109-114.

38. Frank S.L., Klisak I., Sparkes .R.S., Mohandas .Т., Tomlinson J.E., McLean J.W., Lawn. R.M. and Lusis A.J. The apolipoprotein(a) gene resides on human chromosome 6q26-27, in close proximity to the homogeneous gene for plasminogen// Am. J.

39. Hum. Genet.-1998.-V.79.-P.352-356.• v1

40. Fujii S., Sawa H., Saffitz J.E., Lucore C.L., Sobel B.E. Induction of endothelial sell expression of the plasminogen activator inhibitor type 1 gene by thrombosis in vivo// Circulation.-1992.-V.86.-P.2000-2010.

41. Gabel В., Yao Z., Young S.G., Koschinsky M.L. Carboxyl-terminal truncation of apolipoprotein BlOO inhibits lipoprotein(a) particle formation// FEBS Lett.-1994.-V.350.-P.77-81.

42. Gaubatz J.W., Chari M.V., Nava M.L., Guyton J.R. and Morisett J.D. Isolation and characterization of the two major apoproteins in human lipoprotein(a)// J. Lipid. Res.-1987.-V.28.-P.69-79.

43. Gavish D. and Breslow JL. Lipoprotein(a) reduction by N-acetylcysteine// Lancet.-1991.-V.337.-P.203-204.

44. Gaw A., Brown A., Ford I. Impact of apo(a) length polymorphism and the control of plasma Lp(a) concentrations. Evidence for a threshold effect// Arterioscler. Tromb. Vase. Biol.-1998.-V.18.-P.1870-1876.

45. Ghilain J.M., Parfondry A., Kozyreff V. and Heller F.R. Lipoprotein(a), cholesterol and coronary heart disease// Lancet.-1988.-V.2.-P.963.

46. Ghiselli G., Gaddi A., Barozzi G., Clarroc-chi A., Descovich G. Plasma lipoprotein(a) concentration in familial hypercholesterolemi-c patients without coronary artery disease// Metabolism.-1992.-V.41.-P.833-838 .

47. Ginsburg D., Zeheb R., Yang A.Y., Rafferty U.M., Andreasen P. A., Nielsen L. , Dano K., Lebo R.V., Gelehrter Т.О. cDNA cloning of human plasminogen activator inhibitor from endothelial cells// J. Clin. Invest.-1986.-V.78.-P.1673-1680.

48. Ginsburg D. Regulation of PAI-1 gene expression// Thromb. Haemost.-1991.-V.65.-P.740.

49. Grainger D.J., Kirschelohr H.L., Metcalfe J.C., Weissberg P.L., Wade D.P. and Lawn R.M. Proliferation of human smooth muscle cells promoted by lipoprotein(a)// Science.-1993.-V.260.-P.1655-1658.

50. Gries A., Malle E., Wurm H. and Kostner G.M. Influence of dietary fish oils on plasma Lp(a) levels// Thromb. Res.-1990.-V.58.-P.667-668.

51. Guevara J., Knapp R.D., Honda S., Northup S.R. and Morisett J.D. A structural assessment of the apo(a) protein of human lipoprotein (a)// Proteins.-1992.-V.12.-P.188-199.

52. Guevara J., Spurlino J., Jan A.Y., Yang C., Tulinsky A., Prasad B.V., Gaubatz J.W. and Morisett J.D. Proposed mechanismsfor binding of apo {a) kringle type 9 to apoBlOO in human lipoprotein(a)// Biophys. J.-1993.-V.64.-P.68-70.

53. Haberland M.E., Fless G., Scanu A.M. and Folgemann A.M. Modification of Lp(a) by malodialdehyde leads to avid uptake by human monocyte-macrophages// Circulation.-1989.-V.80.-P.11-163.

54. Hajjar K.A., Gavish D., Breslow J.L. and Nachmann R.L. Lipoprotein<a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis// Nature.-1989.-V.339.-P.303-305.

55. Hamsten A., Wiman В., De Faire U., Blomback M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction// N. Engl. J. Med.-1985.-V.313.-P.1557-1563.

56. Hamsten A., De Faire Y., Walldius G. , Dahlen G. , Szamosi A., Landou C., Blomback M., Wiman B. Plasminogen activator inhibitor in plasma. Risk for recurrent myocardial infarction// Lancet.-1987.-V.2.-P.3-9.

57. Hamsten A., Walldus *0., Szamosi A., Blomback M., De Faire U., Dahlen 0., Landou C. and Wiman B. Plasminogen activator inhibitor in plasma// Lancet.-1987.-V.2.-P.3.

58. Harpel P.C., Hermann A., Zhang X., Ostfeld I. and Borth W. Lipoprotein(a), plasmin modulation and atherogenesis// Thromb. Haem.-1995.-V.74.-P.382-386.

59. Hasstedt S.J., Wilson E.E., Edwards C.Q., Cannon W.N., Carmeili D. and Williams R.R. The genetics of quantitative plasma Lp{a): analysis of a large pedigree// Am. J. Med. Genet.-1983.-V.16.-P.169-188.

60. Hearn J.A., Demaio S.J., Roubin G.S., Hammerstorm M. and Sgoutas D. Predictive value of lipoprotein(a) and other serumlipoproteins in angiographic diagnosis of coronary artery disease// Am. J. Cardiol.-1990.-V.66.-P.1176-1180.

61. Hegele R.A., Sutherland S., Robertson M., Wu L., Emi M., Hopkins P.N., Williams R.R. and Lalouel J-M. The effect of genetic determinants of low density lipoprotein levels on lipoprotein{a)// Clin. Invest. Med.-1991.-V.14.-P.146-152.

62. Hegele R.A., Freeman M.R., Langer A., Connelly P.W. and Armstrong P.W. Acute reduction of lipoprotein(a) by tissue-type plasminogen activator// Circulation.-1992.-V.85.-P.2034-2038 .

63. Helmhold M. , Bigge J., Muc-he R. , Mainoo J., Thiery J., Seidel D. and Armstrong V. Contribution of the apo{a) phenotype to plasma Lp(a) concentrations shows considerable ethnic variation// J. Lipid. Res.-1992.-V.32.-P.1919-1928.

64. Hendriks H.F.J., Veenstgra J., Velthuste-Wierik E.J.M., Schaafsma G., Kluft C. Effect of moderate dose of alcohol with evening meal on fibrinolytic factors// BMJ.-1994.-V.308.-P.1003-.1005

65. Hewitt D.J., Milner C., Breckenridge C. and Macguire G. Heritability of "sinking pre-B lipoprotein level: A twin study// Clin. Genet.-1977.-V.11.-P.224-226.

66. Hixon J.E., Britten M.L., Manis G.S. and Rainwater D.L. Apolipoprotein(a) glycoprotein isoforms results from size differences in apo(a) mRNA in baboons// J. Biol. Chem.-1989.-V.264.-P.6013-6016.

67. Ichinose A.,and Kuriyama M. Detection of polymorphisms in the 5'-flanking region of the gene for apolipoprotein(a)// BBRC.-1995.-V.209.-P.372-378.

68. Ikeo К., Takahashi К. and Gojobori Т. Evolutionary origin of numerous kringles in human and simian apolipoprotein(a)// FEBS Lett.-1991.-V.287.-P.14 6-148.

69. Islam S., Gutin В., Smith C., Treiber F. and Kamboh M.I. Association of apolipoprotein(a) phenotypes in children with family history of premature coronary artery disease// Arterioscler. Thromb.-1994.-V.14.-P.1609-1616.

70. Jansson J.J., Nilsson Т.К., Johnson 0. Von Willebrandt factor in plasma: a novel risk for recurrent myocardial infarction and death// Br. Med. J.-1991.-V.66.-P.351-355.

71. Juhan-Vague I., Vague P., Alessi M.C., Badier C., Valadier J., Aillaud M.F., Atlan C. Relationship between plasma insulin, triglyceride, body mass index, and plasminogen activator inhibitor-1// Diabete. Metab.-1987.-V.13.-P.331-336.

72. Juhan-Vague I. and Alessi M.C. Plasminogen activator inhibitor-1 and atherothrombosis// Thromb. Haemost.-1993.-V. 70 .-P.138-143.

73. Juhan-Vague I., Руке S.D.M., Alessi M.C., Jespersen J., Haverkate F., Thompson S.G. Fibrinolytic factor and the risk of myocardial infarction or sudden death in patients with angina pectoris// Circulation.-1996.-V.94.-P.2057-2063.

74. Kamboh M.I., Ferrel R.E. and Kottke B.A. Expressed hypervariable polymorphism of apolipoprotein(a)// Am. J. Hum. Genet.-1991.-V.49.-P.1063-1074.

75. Klausen I.С., Beisiegel U., Menzel H.J., Rosseneu M., Niecaud V. and Faergeman 0. Apo(a) phenotypes and Lp(a) concentrations in offspring of men with and without myocardial infarction// Arterioscler. Tromb. Vase. Biol.-1995.-V.15.-P.1001-1008.

76. Klausen I.C., Sjol A., Hansen P.S., Gerdes L.U., Holler L. , Lemming L., Schroll M., Faergeman 0. Apolipoprotein (a) isoforms and coronary heart disease in men: a nested case-control study// Atherosclerosis.-1997.-V.132.-P.77-84.

77. Kliewer S., Lenhard J., Willson T.M., Patel I., Morris D., Lehmann J. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor у and promotes adipocyte differentiation// Cell.-1995.-V.83.-P.813-819.

78. Koschinsky M.L., Beisiegel U., Henne-Bruns D., Eaton D.L. and Lawn R.M. Apolipoprotein (a) size -heterogenity is related to variable number of repeat sequences in its Mrna// Biochemistry.-1990.-V.29.-P.640-644.

79. Koschinsky M.L., Cote P., Gabel B. and Van der Hoek Y.Y. Identification of the cysteine residue in apolipoprotein(a) thatmediates extracellular coupling with apolipoproteinBlOO// J. Biol. Chem.-1993.-V.268.-P.19819-19825.

80. Kostner G.M. The affection of lipoprotein (a) by lipid lowering drugs// In: Recent aspects of diagnosis and treatment of lipoprotein disorders: impact on prevention ofratherosclerotic diseases/ Alan R. Liss Inc.-1988.-P. 255-263.

81. Kostner G.M., Gavish D., Leopold В., Bolzano K., Weintraub M.S. and Breslow J.L. HMG-CoA-reductase inhibitors lower LDL cholesterol without reducing Lp(a) levels// Circulation.-1989.-V.80.-P.1313-1319.

82. Kraft H-G., Dieplinger H., Hoye E., Utermann G. Lp(a) phenotyping by immunoblotting with policlonal and monoclonal antibodies// Atherosclerosis.-1988.-V.8.-P.212-216.

83. Kraft H-G., Koechl S., Menzel H.J., Sandholzer C., Dtermann G. A transcribed hypervariable locus controlling plasma lipoprotein{a) concentration// Hum. Genet.-1992.-V.90.-P.220-230.

84. Krempler F., Kostner G.M., Bolzano K., and Sandhofer F. Turnover of lipoprotein(a) in man// J. Clin. Invest.-1980.-V.65.-P.1483-1490.

85. Krempler F., Kostner G.M., Haslauer F. and Bolzano K. Studies on the role of specific cell surface receptors in the removal of lipoprotein(a) in man// J. Clin. Invest.-1983.-V.71.-P.1431-1441.

86. Kruithof E.K.O., Tran-Thang C., Ransijn A., Bachmann F. Demonstration of the fast-acting inhibitor of plasminogen activators in human plasma// Blood.-1984.-V.64.-P.907-913.

87. Lackner C., Boerwinkle E., Leffert C.C., Rahming T. and Hobbs H.H. Molecular basis of apolipoprotein(a) isoforms heterogenity as revealed by pulse-field electrophoresis// J. Clin. Invest.-1991.-V.87.-P.2153-2161.

88. Lackner C., Cohen J.C. and Hobbs H.H. Molecular definition of the extreme size polymorphism in apolipoprotein (a)// Hum. Mol. Genet.-1993.-V.2.-P.933-940.

89. Lahiri O.K., Bye S. A non-organic and non-enzymatic extraction method gives higher yields of genomic DNA from whole-blood samples than do nine other methods tested// J. Biochem. Biophys. Meth.-1992.-V.25.-P.193-205.

90. Lawn R.M. Lipoprotein(a) in heart disease// Sci. Am.-1993.-V.4.-P.12-22.

91. Lawn R.M. How often has Lp(a) evolved?// Clin. Genet.-1996.-V.49.-P.167-174.

92. Leerink C.B., Gimpel J.A., Kortlandt W., Bouma B.N. and Rijn van H.J.M. Kinetic analysis of lipoprotein(a) inhibition of plasminogen activation by issue plasminogen activator in vitro// Fibrinolysis.-1991.-V.5.-P.233-238.

93. Lindahl G., Gersdorf E., Menzel H.J., Duba K. , Cleve H., Humphries S. and Utermann G. The gene for the Lp (a)-specific glycoprotein is closely linked to the gene for plasminogen on chromosome 6// Hum. Genet.-1989.-V.81.-P.149-152.

94. Lingenhel A., Kraft H-G, Kotze M., Peeters A.V., Kronenberg F., Kruse R. and Utermann G. Concentrations of the atherogenic Lp (a) are elevated in FH// Eur. J. Hum. Genet.-1998. -V. 6.-P. 5060.

95. Loskutoff D.J., Samad F. The adipocyte and hemostatic balance in obesity: studies of PAI-1// Arterioscler. Thromb. Vase. Biol.-1998.-V.18.-P.1-6.

96. Lucore C.L., Fujii S., Wun T.C., Sobel B.E., Billadello J.J. Regulation of the expression of type 1 plasminogen activator inhibitor in HepG2 cells by epidermal growth factor// J. Biol. Chem.-1988.-V.263.-P.15845-15848.

97. Lucore C.L., Sobel B.E. Interaction of tissue-type plasminogen activator with plasma inhibitors and their-pharmacologic implications// Circulation.-1988/-V.77.-P.660-669.

98. Lyons K.M., Stein J.H. and Smithies O. Length polymorphisms in human proline-rich protein genes generated by intragenic unequal crossing over// Genetics.-1988.-V.120.-P.267-278.

99. Makino K. and Scanu AM. Lipoprotein(a): nonhuman promate models// Lipids.-1991.-V.26.-P.679-683.

100. Malle E., Ibovnik A., Steinmetz A., Kostner G.M. and Sattler W. Identification of: glycoprotein lib as the lipoprotein(a)-binding protein an platelets// Arterioscler. Thromb.-1994.-V.14.-P.345-352.

101. Mann A.W., Kra.ft H-G, Rader D.J., Schaefer J.R., Zech L.A., Gregg R.E., Hoeg J.M. and Brewer H.B. Jr. Human in vivo -catabolism of lipoprotein(a)// Circulation.-1989.-V.80.-P.II-181.

102. Mansfield M.W., Strickland M.H., Carter M.P., Grant P.J. Polymorphisms of the plasminogen activator inhibitor-1 gene in type 1 and type 2 diabetes, and in patients with diabetic retinopathy// Thromb. Haemost.-1994.-V.71.-P.731-736.

103. Marcovina S.M., Zhang Z.H., Gaur V.P. and Albers J.J. Identification of 34 apolipoprotein(a) isoforms: differentialexpression of apolipoprotein(a) alleles between American blacks and whites// BBRC.-1993.-V.191.-P.1192-1196.

104. Marcovina S.M., Lippi G., Bagatell C.J., Bremner W.J. Testosterone-induced supression of lipoprotein(a) in normal men; relation to basal lipoprotein(a) level// Atherosclerosis.-1996.-V.122.-P.89-95.

105. McGill J.В., Schneider D.J., Arfken C.L., Lucore C.L., Sobel B.E. Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients// Diabetes .-1994 .-V.43.-P.104-109.

106. McLean J.W., Tomlinson J.E., Kuang W.J., Eaton D.L., Chen E.Y., Fless G. M. , Scanu A.-M. and Lawn R.M. DNA sequence of human apolipoprotein(a) is homologous to plasminogen// Nature.-1987.-V. 300.-P.132-137.

107. Mehta J., Mehta P., Lawson D., Saldeen Т. Plasma tissue plasminogen activator inhibitor levels in coronary artery disease: correlation with age and serum triglyceride concentrations// J. Am. Coll. Cardiol.-1987.-V.9.-P.263-268.

108. Moss A.J., Goldstein R.E., Marder V.J., Sparks C.E., Oakes

109. E., Sadler ЕГ, Eddy R. and Show's T.B// Am. J. Hum. Genet.-1987.-V.40.-P.338-350.

110. Nestel P., Noakes M., Belling В., McArthur R., Clifton P., Janus E. and Abbey'M. Plasma lipoprotein lipid and Lp(a) changes with substitution of eladic acid for oleic acid in diet// J. Lipid. Res.-1992.-V.33.-P.1029-1036.

111. Nil sson L., Oafvels M., Musakka L., Ensler K., Strickland K., Angelin В., Hamsten A. and Eriksson P. VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor// J. Lipid. Res.-1999.-V.40.-P.913-919.

112. Nilsson Т.К., Johnson 0. The extrinic fibrinolytic system in survivors of myocardial infarction// Thromb. Res.-1987.-V.48.-P.621—630.

113. Ogorelkova M. , Gruber A., Utermann G. Molecular basis of congenital lp(a) deficiency: a frequent apo(a) 'null' mutation in Caucasians// Hum. Mol. Genet.-1999.-V.8.-P.2087-96.

114. Oseroff A., Krishnamurti €., Hassett A., Tang D. , Alving B. Plasminogen activator and plasminogen activator inhibitor activities in men with coronary artery disease// J. Lab. Clin. Med.-1989.-V.113.-P.88-93.

115. Pannekoek H., Veerman H., Lambers H., Diergarde P., Verweij C.L., van Zonneveld A.J., van Mourik J.A. Endothelial plasminogen activator inhibitor (PAI): a new member of the Serpin gene family// EMBO J.-1986.-V.5.-P.2539-2544.

116. Pralong G., Calandra Т., Glauser M.P., Schellekens J., Verhoef J., Bachmann F., Kriuthof E.K.O. Plasminogen activator inhibitor-1: a new prognostic marker in septic shock// Thromb. Haemost.-1989.-V.-61.-P. 459-462.

117. Prins M.H., Hirsh J. A critical review of the relationship between impaired fibrinolysis and myocardial infarction// Amer. Heart. J.-1991.-V.122.-P.54 5-551.

118. Rath M., Niendorf A., Reblin T.M. Dietel M., Krebber H-J. and Beisiegel U. Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients// Atherosclerosis.-1989.-V.9.-P.579-592.

119. Rath M. and Pauling L. Hypothesis: lipoprotein (a) is a surrogate for ascorbate// Proc. Natl. Acad. Sci.-1990.-V.87.-P.6204-6207.

120. Ren S., Man R.Y.K., Angel A., Shen G.X. Oxidative modification enhances lipoprotein(a)-induced overproduction of plasminogen activator inhibitor-1 in cultured vascular endothelial cells// Atherosclerosis.-1997.-V.128.-P.1-10.

121. Rhoads G.G., Dahlen G.H., Berg K., Morton N.'E. and Dannenberg A.L. Lp{a) lipoprotein as a risk factor for myocardial infarction// JAMA.-1986.-V.256.-P.2540-2544.

122. Riccio A., Lund L.R., Sartorio R. , -Lania A., Andreasen P.A., Dano K., Blasi F. The regulatory region of the human plasminogen activator inhibitor type-1 (PAI-1) gene// Nucleic. Acids. Res.-1988.-V.16.-P.2805-2824.

123. Ridker P.M., Hennekens C.H. and Stampfer M.J. A prospective study of lipoprotein (a) and the risk of myocardial infarction// Atherosclerosis.-1992.-V.92.-P. 123-12 9.

124. Ridker P.M., Hennekens C.H., Stampfer M.J. A prospective study of lipoprotein (a) and the risk of myocardial infarction// JAMA.-1993.-V.270.-P.2195-2199.

125. Ritter M.M., Suehler K., Richter W. and Schwandt P. Short and long-term effects of LDL-apheresis on lipoprotein (a) serum levels// Clin. Chem. Acta.-1990.-V.195.-P.9-16.

126. Ross R. The process of atherogenesis cellular and molecular interaction: from experimental animal models to humans// Diabetologia.-1992.-V.35(suppl.2).-P.S34-S40.

127. Rouy D., Grailhe P. , Nigon F., Chapman J. and Angles-Cano E. Lipoprotein(a) impaires generation of plasmin by fibrin-bound tissue-type plasminogen activator// Arterioscler. Thromb.-1991.-V.11.-P.629-638.

128. Samad F. and Loskutoff D.J. Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice// Mol. Med.-1996.-V.2.-P.568-582.

129. Sandholzer C., Feussner G., Brunzell J. and Utermann G. Distribution of apolipoprotein(a) in the plasma from patients with lipoprotein lipase deficiency and with type III hyperlipoproteinemia// J. Clin. Invest.-1992.-V.90.-P.1958-1965 .

130. Sawa H., Fujii S., Sobel B.E. Augmented arterial wall expression of type I plasminogen activator inhibitor induced by thrombosis// Arterioscler. Thromb.-1992.-V.12. -P.1507-1515.

131. Schneiderman J., Sawdey M.S., Keeton M.R., Bordin G.M., Bernstein E.F., Dilley R.B., Loskutoff D.J. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries// Proc. Natl. Acad. Sci.-1992.-V.89.-P.6998-7002.

132. Sprengers E.D. and Kluft C. Plasminogen activator inhibitors// Blood.-1987.-V.69.-P.381-387.

133. Sprengers E.D., Akkerman J.W.N., Jansen B.G. Blood platelet plasminogen activator inhibitor : two different pools of endothelial cell type plasminogen activator inhibitor in human blood// Thromb. Haemost.-1986.-V.55.-P.325.

134. Swallow D.M., Gendler S., Griffith В., Corney G., Taylor-Papadimitriou J. and Bramwell M.E. The human tumor-associatedepothelium mucins are coded by an expressed hypervariable gene locus PUM// Nature.-1987.-V.328.-P.82-84.

135. Takada Y., Takada A. Plasma levels of t-PA free PAI-1 and a complex of t-PA with PAI-1 in human males and females at various ages// Thromb. Res.-1989.-V.55.-P.601-609.

136. Takahashi Y., Tanaka Т., Minowa H., Ookubo Y., Sugimoto M., Nakajima M., Miyauchi Y., Yoshioka A. Hereditary partial deficiency of plasminogen activator inhibitor-1 associated with a lifelong bleeding tendency// Int. J. Hematol.-1996.-V.64.-P.61-68.

137. Taskinen M.R., Puolakka J., Pyorala Т., Luotola H., Bjoern M., Kaariainen J., Lahdenpera S. and Ehnholm C. Hormone replacement therapy lowers plasma ' Lp(a) concentrations// Arterioscler. Thromb. Vase. Biol.-1996.-V.16.-P.1215-1221.

138. Terres W., Krewitt M., Hamm C.W. Effects of lipoprotein(a) in vitro lysis of whole blood thrombi from healthy volunteers// Thromb. Res.-1993.-V.69.-P.479.

139. Tholstrup Т., Marckmann P., Vessby B. and Sandstoerm B. Effect of fats high in individual satureated fatty acids onplasma lipoprotein(a) levels in young healthy men// J. Lipid. Res.-1995.-V.36.-P.1147-1452.

140. Utermann G., Menzel H.J., Kraft H-G., Duba H.C., Kernmler H.G. and Seit C. Lp( a) glycoprotein phenotypes.' Inheritance and relation to Lp(a)-lipoprotein concentrations i-n plasma// J. Clin. Invest.-1987.-V.80.-P.458-465.

141. Utermann G., Duba C. and Menzel H.J. Genetics of the quantitative Lp(a) lipoprotein trait. II. Inheritance of Lp(a) glycoprotein phenotypes// Hum. Genet.:-1988 .-V. 78 .-P. 4 7-50.

142. Utermann G. The mysteries of lipoprotein(a)// Science.-1989.-V.246.-P.904-910.

143. Utermann G. and Kraft H-G. Lipoprotein(a) in cirrhosis// BMJ.-1992.-V.305.-P.185.

144. Van den Ende A., van der Hoek Y.Y., Kastelein J. J.P., Koschinsky M.L., Labeur C., Rosseneu M. Lipoprotein(a)// Adv. Clin. Chem.-1996.-V.32.-P.73-134.

145. Van der Berg J.L., Weitkamp L., Kammers C.M., Weill P., Aivaliotis M.J. and Rainwater D.L. Linkage of plasminogen (pig)and apolipoprotein(a) (Lpa) in baboons// Genomics.-1991.-V.11.-P.925-930.

146. Van der Hoek Y.Y., Wittekoek M.E., Beisiegel U., Kastelein J.J. and Koschinsky M.L. The apolipoprotein(a) kringle IV repeats which differ from the major repeat kringle are present in variable-sized isoforms// Hum. Mol. Genet.-1993.-V.2.-P.361-366.

147. Vanderkerckhove Y., Baele G., De Puydt H., Weyne A. , Clement D. Plasma tissue plasminogen activator levels in patients with coronary heart disease// Thromb. Res.-1988.-V.50.-P.44 9-453 .

148. Van Meijer M., Pannekoek H. Structure of plasminogen activator inhibitor ! (PAI-1) and it's function in fibrinolysis: an update// Fibrinolysis.-1995.-V.9.-P.263-27 6.

149. Vague P., Juhan-Vague I., Alessi M.C., Badier C., Valadier J. Metformin decrease the high plasminogen activator capacity, plasma insulin and triglyceride levels in non-diabetic obese subjects// Thromb. Haemost.-1987.-V.57.-P.326-328.

150. Wade D.P., Clarke J.G., Lindahl A.C., Liu B.R., Zysow B.R., Meer K. , Schwartz K., and Lawn R.M. Genetic influences on lipoprotein(a) concentration// Biochem. Soc. Trans.-1993.-V.21.-P. 4 99-502.

151. Wade D.P., Clarke J.G., Lindahl A.C., Liu B.R., Zysov B.R., Meer K., Schwartz K., Lawn R.M. 5' control regions of the.apolipoprotein(a) gene and members of the related plasminogen family// Proc. Nat. Acad. Sci.-1993.-V.90.-P. 1369-1373.

152. Wade D.P., Puckey L.H., Knight B.L. , Acquati F., Mihalich A. and Taramelli R. Characterization of multiple enhanser regions upstream of the apolipoprotein(a) gene// J. Biol. Chem.-1997.-V.2-8.-P.30387-30399.

153. Wang X.L., Wilcken D.E.L. and Dudman N.P.B. Early expression of the apolipoprotein(a) gene: relationship between infants and their parents serum apolipoprotein (a) levels// Pediatrics.-1992.-V.89.-P.401-406.

154. Wanner C., Rader D. , Bartens W., Kramer J., Brewer H.B., Schollmeyer P. and Wieland H. Elevated plasma lipoprotein (a): in patients with the nephrotic syndrome// Ann. Intern. Med.-1993.-V.119.-P.263-269.

155. Wasylyk В., Hahn S.L., Giovane A. The ETS family of transcription factors// Eur. J. Biochem.-1993.-V.211.-P. 7-1в .

156. Wiman В., Almquist A., Sigurdardottir 0., Lindahl T. Plasminogen activator inhibitor 1 (PAI) is bound to vitronectin in plasma// FEBS Lett.-1988.-V.242.-P.125-128.

157. Zenker G., Koltringer P., Bone G. , Niederkorn K. , Pfeiffer K. and Jurgens G. Lipoprotein(a) as a strong indicator for cerebrovascular disease// Stroke.-1986.-V.17.-P.942-945.

158. Zidovetzki R. , Chen P., Fisher M., Hofman F.M. NicotineVincreases plasminogen activator inhibitor-1 production by human brain endothelial cells via protein kinase C-associated pathway// Stroke.-1999.-V.30.-P.651-655.

159. Zysov В., Lindahl G. , Wade D. , Knight В., Lawn R. C/T polymorphism in the 5' untranslated region of the apolipoprotein(a) gene introduces an upstream ATG and reduces in vitro translation// Arterioscler. Tromb. Vase. Biol.-1995.-V.15.-P.58-64.