Apolipoproteins, Reverse Cholesterol Transport and Coronary Heart Disease

  • G. Assmann
  • A. von Eckardstein
  • H. Funke
Part of the Argenteuil Symposia book series (ARGENTEUIL)

Abstract

Several epidemiological and clinical studies revealed an inverse correlation between low plasma concentrations of high-density lipoprotein (HDL) cholesterol as well as its major protein component apolipoprotein A-I (apo A-I) and the risk of myocardial infarction (reviewed in Gordon and Rifkind 1989). Family and twin studies suggested partial heredity of low HDL cholesterol levels and have put the influence of genes at 35%-50% (Hunt et al. 1989; Assmann et al. 1989a). Frequently, familial HDL cholesterol deficiency was paralleled with a family history of premature coronary heart disease (CHD) (Pometta et al. 1979; DeBacker et al. 1986). Thus, a causal role between low levels of HDL cholesterol and coronary risk appears well established. However, the pathophysiological relationship between decreased serum concentrations of HDL cholesterol and the development of coronary heart disease has still remained obscure. The reverse cholesterol transport model (Glomset 1968) is most widely used to explain the role of HDL in lipid metabolism and in atherogenesis. HDL precursors, so-called nascent HDL or HDL disks, are generated through lipolysis of chylomicrons and VLDL as well as by direct secretion of the liver (reivewed in Brunzell 1989 and Assmann et al. 1989b). HDL subclasses and reconstituted HDL-like particles that contain apo A-I were shown to take up excess cellular cholesterol by interaction with specific cell surface recognition sites (reviewed in Assmann et al. 1989b). Upon esterification of free cholesterol by lecithin:cholesterol acyltransferase (LCAT), the core of small and dense HDL particles becomes enriched in cholesterol esters and their particle size increases (reviewed in Norum et al. 1989).

Keywords

Cholesterol Codon Lipase Cysteine Anemia 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Assmann G, Schulte H, Funke H, von Eckardstein A, Seedorf U (1989a) The prospective cardiovascular Münster (PROCAM) study: identification of high-risk individuals for myocardial infarction and the role of HDL. In: Miller NE (ed) High density lipoproteins and atherosclerosis IL Exerpta Medica, Amsterdam, pp 51–60Google Scholar
  2. Assmann G, Schmitz G, Brewer HB (1989b) Familial high density lipoprotein deficiency: tangier disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill Information Services, New York, pp 1267–1282Google Scholar
  3. Assmann G, Schmitz G, Funke H, von Eckardstein A (1990) Apolipoprotein A-I and HDL deficiency. In: Mahley RW, Utermann G (eds) Current opinion in lipidology. Vol 1, no. 2: Genetics and molecular biology. Current Sciences, London, pp 110–115Google Scholar
  4. Bazri S, Korn ED (1973) Single bilayer liposomes prepared without sonication. Biochim Biophys Acta 298:1015–1019CrossRefGoogle Scholar
  5. Breslow JL (1989) Familial disorders of high density lipoprotein metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill Information Services, New York, pp 1251–1266Google Scholar
  6. Brunzell JD (1989) Familial lipoprotein lipase deficiency and other causes of the chylomicronemia syndrome. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill Information Services, New York, pp 1165–1180Google Scholar
  7. Carlsson LA, Holmquist L (1985a) Evidence for the presence in human plasma of lecithin:cholesterol acyltransferase activity (ß-LGAT) specifically esterifying free cholesterol of combined pre-β-and β-lipoproteinsin. Acta Med Scand 218:197–205CrossRefGoogle Scholar
  8. Carlsson LA, Holmquist L (1985b) Evidence for deficiency of high density lipoprotein lecithin:cholesterol acyltransferase activity (α-LCAT) in fish-eye disease. Acta Med Scand 218:189–196CrossRefGoogle Scholar
  9. Carlsson LA, Holmquist L, Assmann G (1987) Different substrate specificities of plasma lecithin:cholesterol acyltransferase in fish eye disease and Tangier disease. Acta Med Scand 222:283–289Google Scholar
  10. DeBacker G, Hulstaerdt F, DeMunck K, Rosseneu M, Van Parijs L, Dramaix M (1986) Serum lipids and apolipoproteins in students whose parents suffered from a myocardial infarction. Am Heart J 112:478–484CrossRefGoogle Scholar
  11. Dobiasova M (1983) Lecithin: cholesterol acyltransferase and the regulation of endogenous cholesterol transport. Adv Lipid Res 20:107–144PubMedGoogle Scholar
  12. Forte TM, Nichols AV, Krauss RM, Norum RA (1984) Familial apolipoprotein A-I and C-ffl deficiency: subclass distribution, composition and morphology of lipoproteins in a disorder associated with premature atherosclerosis. J Clin Invest 74:1601–1613PubMedCrossRefGoogle Scholar
  13. Franceschini G, Baio M, Calabresi L, Sirtor CR, Cheung MC (1990) Apolipoprotein A-I(Milano): partial familial lecithin cholesterol acyltransferase deficiency. Biochim Biophys Acta 1043:1–6PubMedGoogle Scholar
  14. Frohlich J, McLeod R, Pritchard PH, Fesmire J, McConathy W (1988) Plasma lipoprotein abnormalities in heterozygotes for familial lecithin: cholesterol acyltransferase deficiency. Metabolism 37:3–8PubMedCrossRefGoogle Scholar
  15. Funke H, von Eckardstein A, Pritchard PH, Karas M, Albers JJ, Assmann G (1991) A frameshift mutation in the apo A-I gene causes corneal opacities, HDL deficiency and partial LCAT deficiency. J Clin Invest 87:375–380CrossRefGoogle Scholar
  16. Glomset JA (1968) The plasma lecithin:cholesterol acyltransferase reaction. J Lipid Res 9:155–163PubMedGoogle Scholar
  17. Gordon D, Rifkind BM (1989) Current concepts: high density lipoproteins-the clinical implications of recent studies. N Engl J Med 321:1311–1315PubMedCrossRefGoogle Scholar
  18. Hunt SC, Hasstedt SJ, Kuida H, Stults BM, Hopkins PN, Williams RR (1989) Genetic heritability and common environmental components of resting and stressed blood pressures, lipids, and body mass index in Utah pedigrees and twins. Am J Epidemiol 129:625–638PubMedGoogle Scholar
  19. Jonas A, von Eckardstein A, Kezdy K, Steinmetz A, Assmann G (1991) Structural and functional properties of reconstituted high density lipoprotein discs prepared with six apolipoprotein variants. J Lipid Res 32:90–100Google Scholar
  20. Nichols WC, Dwulet F, Liepnieks J, Benson MD (1988) Variant apolipoprotein AI as a major constitutent of a human hereditary amyloid. Biochem Biophys Res Commun 156:762–768PubMedCrossRefGoogle Scholar
  21. Norum KR, Gjone E, Glomset JA (1989) Familial lecithin:cholesterol acyltransferase deficiency including fish-eye disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill Information Services, New York, pp 1181–1194Google Scholar
  22. Pometta D, Micheli H, Suenram A, Jornot C (1979) HDL lipids in close relatives of coronary heart disease patients: environmental and genetic influences. Atherosclerosis 34:419–429PubMedCrossRefGoogle Scholar
  23. Pritchard PH, McLeod R, Frohlich J, Park MC, Kudchodkar BJ, Lacko AG (1988) Lecithin cholesterol acyltransferase in familial HDL deficiency (Tangier disease). Biochim Biophys Acta 958:227–234PubMedGoogle Scholar
  24. Utermann G, Schoenborn W, Langer KH, Dieter P (1972) Lipoproteins in LCAT-deficiency. Hum Genet 16:295–302CrossRefGoogle Scholar
  25. von Eckardstein A, Funke H, Henke A, Altland K, Benninghoven A, Assmann G (1989) Apolipoprotein A-I variants: naturally occurring substitutions of proline residues affect the plasma concentration of apolipoprotein A-I. J Clin Invest 84:1722–1730CrossRefGoogle Scholar
  26. von Eckardstein A, Funke H, Walter M, Atland K, Benninghoven A, Assmann G (1990) Structural analysis of apolipoprotein A-I variants: amino acid substitutions are nonrandomly distributed throughout the apolipoprotein A-I primary structure. J Biol Chem 265:8610–8617Google Scholar
  27. Wilson DE, Emi M, Iverius PH et al. (1990) Phenotypic expression of heterozygous lipoprotein lipase deficiency in the extended pedigree of a proband heterozygous for a missense mutation. J Clin Invest 86:735–750PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 1992

Authors and Affiliations

  • G. Assmann
  • A. von Eckardstein
  • H. Funke

There are no affiliations available

Personalised recommendations