Apolipoproteins are of considerable physiological importance and are associated with various disorders, including dyslipidemia and cardiovascular and neurodegenerative diseases. Apolipoproteins have therefore emerged as key risk markers and important research targets, yet their functions have not been fully elucidated.
Apolipoproteins are proteins that bind to and help solubilize hydrophobic lipids in the blood. Together with phospholipids, apolipoproteins form lipoprotein particles into which different lipids can be packed. Apolipoproteins have pivotal functions as structural components in lipoprotein particles, as ligands for receptors, and as co-factors for enzymes. Lipoprotein particles are necessary for transportation of lipids used for energy and for synthesis of hormones, vitamins, and bile acids. The apolipoproteins apoB and apoE are important in the transport of dietary and endogenous lipids to the peripheral tissues where these lipids are used as an energy source, whereas apoA1 is crucial for returning excess cholesterol from peripheral tissues to the liver. Apolipoproteins also have an essential role in neurological processes; for example, apoE and apoJ are involved in the transportation of lipids in the brain. Other apolipoproteins, such as apoH, apoD, and apoM, have not been thoroughly investigated and their functions remain to be elucidated.
Apolipoproteins are components of different lipoproteins and can be defined as non-exchangeable or exchangeable. ApoB is non-exchangeable and anchored in the lipoprotein article whereas apoA1, apoE, apoD, apoJ, apoH, and apoM are exchangeable and can be transferred between different lipoprotein particles. ApoA1 and apoB represent the main protein components of HDL and LDL, respectively.There are two forms of apoB: apoB-100 and apoB-48. ApoB-100 is produced in the liver and is incorporated into LDL whereas apoB-48 is produced in the intestine as a component of chylomicrons. ApoB-100 mediates ligand–receptor uptake of LDL, and approximately 98% of plasma apoB is in this form. ApoE is mainly present in VLDL and HDL. The high-density HDL particle contains large amounts of proteins as well as apoD, apoM, apoH, and apoJ; however, these apolipoproteins can also be associated with other lipoproteins and ApoH can circulate in its free form.
Apolipoprotein involvement in disease
The association between apolipoproteins and different diseases is well known. For example, apoA1 and apoB are associated with cardiovascular diseases and apoE and apoJ with Alzheimer’s disease. ApoD has been reported to have a role in several different neurological disorders including schizophrenia and Alzheimer’s disease as well as in lipid disorders such as the metabolic syndrome and diabetes. ApoH, also known as beta 2 glycoprotein I, is involved in autoimmune diseases such as antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Recently apoM has been implicated in the pathogenesis of atherosclerosis, diabetes, and renal diseases, and polymorphism in the apoM gene is associated with coronary artery disease and diabetes. Consequently, apolipoproteins have emerged as key risk markers to predict and diagnose different diseases, and techniques to measure apolipoprotein levels are important tools in clinical routine and research.