A cell culture system was employed to test a large number of samples of human serum for the ability to stimulate the efflux of cell cholesterol. The extent of efflux obtained with each specimen was correlated with the serum concentrations of cholesterol, triglycerides, apoprotein (apo) B, apo A-I, apo A-II, and lipoprotein subfractions (ie, high-density lipoprotein 2 [HDL 2 ], HDL 3 , lipoprotein [Lp] A-I, and LpA-I:A-II). In addition, the subsequent esterification of the released cholesterol and the distribution of the synthesized exogenous cholesteryl esters between HDL and low-density lipoprotein/ very-low-density lipoprotein provided estimates of the lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities of each serum. The values for these activities were analyzed for correlations with cell efflux and the various serum parameters. Cell cholesterol efflux best correlated with serum total HDL cholesterol values. HDL 2 and HDL 3 correlated about equally well with efflux, whereas LpA-I demonstrated a much greater association with T he process by which cholesterol in peripheral tissues is transported back to the liver for excretion has been termed reverse cholesterol transport (RCT). While the importance of high-density lipoprotein (HDL) in RCT is now universally accepted, it is not known which specific fractions of HDL are most important. Most in vitro studies have used either native lipoproteins, particularly subclasses of HDL, or reconstituted particles containing apolipoproteins and phospholipids to study cholesterol efflux, which is the first step in RCT. The difficulties in clearly identifying the specific lipoprotein in serum or interstitial fluid that plays the primary role in cholesterol efflux are due to several facts. First, there is a wide variety of particles within the HDL class of lipoproteins, and no single class of particles appears to be uniquely responsible for cholesterol efflux. 1 -2 Second, depending on the method of separation, two subclasses of HDL have been pro- Studies with whole serum have been limited, and it is not known if the quantification of a single serum parameter, or even combinations of parameters, is sufficient to allow the prediction of how individual samples of human serum will influence cellular cholesterol efflux.Cholesterol efflux studies using whole sera are best represented by the investigations of Fielding and colleagues. 68 The initial studies using fibroblasts as the cholesterol donor cell clearly established that sera from individuals differed in their ability to produce changes in net cellular cholesterol efflux. These differences were correlated to a number of clinical conditions that are known to influence serum lipoprotein patterns, such as by guest on May 9, 2018 http://atvb.ahajournals.org/ Downloaded from

BackgroundAirborne pollution is a rising concern in urban areas. Epidemiological studies in humans and animal experiments using rodent models indicate that gestational exposure to airborne pollution, in particular diesel engine exhaust (DE), reduces birth weight, but effects depend on exposure duration, gestational window and nanoparticle (NP) concentration. Our aim was to evaluate the effects of gestational exposure to diluted DE on feto-placental development in a rabbit model.Pregnant females were exposed to diluted (1 mg/m3), filtered DE (NP diameter ≈ 69 nm) or clean air (controls) for 2 h/day, 5 days/week by nose-only exposure (total exposure: 20 days in a 31-day gestation).ResultsDE exposure induced early signs of growth retardation at mid gestation with decreased head length (p = 0.04) and umbilical pulse (p = 0.018). Near term, fetal head length (p = 0.029) and plasma insulin and IGF1 concentrations (p = 0.05 and p = 0.019) were reduced. Placental function was also affected, with reduced placental efficiency (fetal/placental weight) (p = 0.049), decreased placental blood flow (p = 0.009) and fetal vessel volume (p = 0.002). Non-aggregated and “fingerprint” NP were observed at various locations, in maternal blood space, in trophoblastic cells and in the fetal blood, demonstrating transplacental transfer. Adult female offspring were bred with control males. Although fetoplacental biometry was not affected near term, second generation fetal metabolism was modified by grand-dam exposure with decreased plasma cholesterol (p = 0.008) and increased triglyceride concentrations (p = 0.015).ConclusionsRepeated daily gestational exposure to DE at levels close to urban pollution can affect feto-placental development in the first and second generation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0151-7) contains supplementary material, which is available to authorized users.