High density lipoprotein historical perspective

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]


The discovery of HDL dates back to 1929 when Michel Macheboeuf isolated α-globulin from horse serum in the Pasteur Institute.[1] This lipoprotein was identified as an alpha lipoprotein and was later referred to as HDL. The classification of lipoproteins into alpha and beta referring to HDL and LDL respectively led to a further understanding of lipoproteins.[2] For a long time, LDL and its association with cardiovascular outcomes were the focus of research studies. However, the discovery that HDL is not as simple as it was thought in terms of structure and function fueled research with more studies about this complex lipoprotein. One of the earliest association between HDL level and cardiovascular risks was hypothesized in the mid 1970's.[3] The Framingham Heart Study and the Helsinki Heart Study were among the landmark studies that confirmed this association in the late 1980's.[4][5]

Historical Perspective

  • In 1929, Michel Macheboeuf isolated the first lipoprotein from horse serum. A stable, water-soluble α-globulin was precipitated from a 50% neutral ammonium sulfate-treated horse serum and was later identified as HDL.[1]
  • Further understanding of the nature of lipoproteins was driven by the laboratories efforts to purify blood for transfusion during World War II. Lipoproteins were classified into "alpha-lipoprotein" and "beta-lipoprotein" referring to HDL and LDL respectively.[2]
  • HDL was initially thought to be as simple in structure as LDL. Insight about the complexity and heterogeneity of HDL began later on after the discovery that HDL has several constituent proteins.
  • In an article published in The Lancet in 1975, scientists hypothesized the association between low HDL level and high cardiovascular risk based on the finding that body cholesterol pool increases as HDL decreases.[3] The association between low HDL and cardiovascular risk factors was thoroughly investigated in The Framingham Heart Study and The Helsinki Heart Study in the late 1980's.[4][5]


  1. 1.0 1.1 Olson RE (1998). "Discovery of the lipoproteins, their role in fat transport and their significance as risk factors". J Nutr. 128 (2 Suppl): 439S–443S. PMID 9478044.
  2. 2.0 2.1 Gotto AM (2005). "Evolving concepts of dyslipidemia, atherosclerosis, and cardiovascular disease: the Louis F. Bishop Lecture". J Am Coll Cardiol. 46 (7): 1219–24. doi:10.1016/j.jacc.2005.06.059. PMID 16198834.
  3. 3.0 3.1 Miller GJ, Miller NE (1975). "Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease". Lancet. 1 (7897): 16–9. PMID 46338.
  4. 4.0 4.1 Wilson PW, Abbott RD, Castelli WP (1988). "High density lipoprotein cholesterol and mortality. The Framingham Heart Study". Arteriosclerosis. 8 (6): 737–41. PMID 3196218.
  5. 5.0 5.1 Mänttäri M, Elo O, Frick MH, Haapa K, Heinonen OP, Heinsalmi P; et al. (1987). "The Helsinki Heart Study: basic design and randomization procedure". Eur Heart J. 8 Suppl I: 1–29. PMID 3322826.

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