It has been reported to facilitate the exchange of phospholipids, unesterified cholesterol, diacylglycerides, vitamin E

(tocopherols), and lipopolysaccharides (LPS) between plasma lipoproteins, with functional consequences in vascular biology, brain physiology, reproductive biology, inflammation, and innate immunity.1 In plasma, PLTP is mainly transported by high-density lipoproteins (HDLs), and previous studies of PLTP focused on HDL. Earlier studies in mouse models provided direct support for an HDL-orientated function of PLTP, that is, with higher2 or lower3-5 levels of HDL cholesterol in transgenic mice overexpressing human PLTP and lower HDL cholesterol levels in PLTP-deficient mice.6 In fact, there is growing evidence that PLTP plays a pivotal role in HDL-mediated reverse cholesterol Bortezomib in vivo transport because of its ability (1) to generate nascent, preβ-HDL (i.e., the primary acceptors of cell-derived cholesterol), which dissociates from the surface of very-low-density lipoproteins (VLDLs) during lipolysis,7 (2) to form both preβ-HDL and large HDL2-like particles through intra-HDL remodeling,8-10 and (3) to facilitate cholesterol and phospholipid efflux from peripheral cells through an ABCA1-dependent pathway in the initiating step of reverse cholesterol

transport11-13 (see Fig. this website 1). Recent genome-wide association studies brought evidence of the association of higher PLTP transcript levels in the liver with higher HDL cholesterol concentrations.14 However, beyond PLTP gene-expression levels, the consequences of plasma PLTP activity might be highly dependent on the metabolic context and on the plasma lipoprotein profile. VDA chemical For instance, plasma PLTP activity was found

to be inversely associated with HDL-cholesterol levels, but positively associated with apolipoprotein B (apoB) levels in a cohort of Chinese patients who underwent diagnostic coronary angiography.15 HDL; high-density lipprotein; LPS, lipopolysaccharides; PLTP, phospholipid transfer protein; VLDL, very-low-density lipoprotein. In wild-type mice, most of the plasma cholesterol is transported in the HDL fraction, with smaller amounts of cholesterol in VLDL and barely detectable amounts of cholesterol in the low-density lipoprotein (LDL) fraction. It is a major limitation of the mouse model, because plasma lipoprotein profiles in humans and rabbits normally display prominent non-HDL, apoB-containing lipoproteins. Interestingly, mice genetically engineered to have a human-like plasma lipoprotein profile (in particular, with human apoB synthesis in the liver and similar plasma apoB levels to those in humans) and expressing a PLTP-deficiency trait revealed a new, unexpected role of PLTP: the ability to increase both the liver production rate and plasma levels of apoB-containing lipoproteins.