High-density lipoprotein metabolism, composition, function, and deficiency.
OBJECTIVE
To examine the recent advances in our knowledge of HDL metabolism, composition, function, and coronary heart disease (CHD), as well as marked HDL deficiency states because of mutations in the apolipoprotein (apo) A-I, ATP-binding cassette transfer protein A1 and lecithin cholesterol acyltransferase (LCAT) gene loci.


RESULTS
It has been documented that apoA-I, myeloperoxidase and paraoxonase 1 (PON1) form a complex in HDL that is critical for HDL binding and function. Myeloperoxidase has a negative impact on HDL function, whereas PON1 has a beneficial effect. Patients who lack apoA-I develop markedly premature CHD. Patients who lack ATP-binding cassette transfer protein A1 transporter function have only very small discoidal preβ-1 HDL, and develop hepatosplenomegaly, intermittent neuropathy and premature CHD, although significant heterogeneity for these disorders has been reported. Patients with LCAT deficiency have abnormal small discoidal LDLs and HDL particles, and develop kidney failure. Enzyme replacement therapy is being developed for the latter disorder.


CONCLUSIONS
Recent data indicates that proteins other than apoA-I and apoA-II such as MPO and PON1 have important effects on HDL function. There has been considerable recent progress made in our understanding of HDL protein content and function.
Lipid Metabolism Section, Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA.
Ernst J
EJ
Schaefer
Pimjai
P
Anthanont
Bela F
BF
Asztalos
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism; D003327:Coronary Disease / Q000235:genetics / Q000378:metabolism; D056426:Genetic Loci; D006801:Humans; D052456:Hypoalphalipoproteinemias / Q000235:genetics* / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000235:genetics* / Q000378:metabolism*; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D009195:Peroxidase; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human