Genetic Mutations Affecting Human Lipoproteins, Their Receptors, and Their Enzymes

Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia

“…ApoE is a major constituent of very low-density lipoproteins and is an essential ligand 4 for the uptake and clearance of atherogenic lipoproteins, playing important roles in atherosclerosis by modifying inflammatory responses and facilitating cholesterol efflux from foam cells (10,11). ApoA1 is a major apolipoprotein of high-density-lipoprotein cholesterol (HDL-C) and is significantly involved in the regulation of lipid transport and metabolism of HDL-particles (12). ApoAI binding protein (AIBP) is secreted from tissue and physically binds with apoAI (13).…”

The Effects of Mutations in Helices 4 and 6 of ApoA-I on Scavenger Receptor Class B Type I (SR-BI)-mediated Cholesterol Efflux Suggest That Formation of a Productive Complex between Reconstituted High Density Lipoprotein and SR-BI Is Required for Efficient Lipid Transport

“…Apolipoprotein A-I (apoA-I) 1 is the major protein constituent of high density lipoprotein (HDL) and plays crucial roles in the synthesis, structure, and functions of HDL (1). ApoA-I undergoes gradual extracellular lipidation by the action of ABCA-1 (2)(3)(4)(5), leading to the formation of pre-␤1, discoidal pre-␤2, and spherical ␣-HDL particles (6 -9).…”

Pleiotropic Functions of HDL Lead to Protection from Atherosclerosis and Other Diseases

“…Most of the mutations affect the interaction of apoA-I with LCAT. Eight mutations between residues 26 and 107 and one on residue 173, have been associated with amyloidosis and low HDL levels (Sorci- Thomas and Thomas, 2002;Zannis et al, 1993) and one mutation on residue 164 is associated with increased risk for ischemic heart disease and reduced life expectancy (Haase et al, 2011). The in vivo interactions of representative naturally occurring apoA-I mutants with LCAT were studied by adenovirusmediated gene transfer in apoA-I deficient mice.…”