Epidemiological studies show a strong inverse relationship between HDL levels (HDL cholesterol or apo-A1) and risk of CHD. Even a small increase in HDL is significantly correlated with a reduction in the risk of premature heart disease.
Unlike VLDL and chylomicrons, HDL is formed from its protein and lipid components in the bloodstream and interstitial fluids. The major apolipoproteins of HDL are apo-A1 and apo-A2. These proteins are secreted from hepatocytes and intestinal epithelial cells independently and also as minor components of VLDL and chylomicrons. Apo-A1 and apo-A2 bind to phospholipids. Phospholipids are available from the surface of VLDL after lipolysis. In addition, cells are able to efflux phospholipids through the action of ABCA1.
ABCA1 is a membrane transport protein belonging to a large family of ATP-binding cassette proteins. These proteins include the cystic fibrosis transmembrane receptor, the sulfonylurea receptor (a pancreatic β-cell protein involved in insulin secretion), and the multidrug resistance transporter proteins. It is thought that ABCA1 mediates the efflux of phospholipid and/or cholesterol from cells, thus making them available for association with apolipoproteins to form HDL. Its crucial role in this process was established by the discovery that two types of severe inherited HDL deficiency syndromes are caused by mutations in ABCA1 (see Fig. 12).
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