Effects Of Conserved Proline Apoai Variants On Hdl Structure And Function

Abstract

Background and Aims: Although plasma high density lipoproteins (HDL) and apolipoprotein (apo) AI levels negatively correlate with atherosclerotic cardiovascular disease (CVD), most HDL-raising interventions do not reduce CVD events. Moreover, other studies show that HDL function, e.g., support of macrophage cholesterol efflux, may be more important than the plasma HDL levels. HDL instability is relevant to the activities of plasma LCAT, CETP, PLTP, SR-BI, and HL. The mechanisms and pathways underlying the HDL biogenesis determine its compositions and ultimately its function in vivo. Alignment of the α-helices of apo AI, reveals highly conserved amino acid residues across 31 species. Moreover, proline-initiated amphipathic a-helices are a conserved structural motif among the exchangeable apos. We tested the hypothesis that highly conserved amino acid residues in apo AI are essential to its structure and function.