Overexpression of apolipoprotein (apo) AIV in transgenic mice confers significant protection against atherosclerosis apoE knockout animals even the presence a more severe atherogenic lipid profile. Because lipoprotein oxidation has been recognized to be pivotal development atherosclerosis, antioxidative activity apoAIV was investigated. Fasting intestinal lymph used mimic conditions interstitial fluid, potential site for vivo. ApoAIV (10 μg/ml) significantly inhibited copper-mediated lymph....

HDLs are a family of heterogeneous particles that vary in size, composition, and function. The structure most is maintained by two scaffold proteins, apoA-I apoA-II, but up to 95 other "accessory" proteins have been found associated with the particles. Recent evidence suggests these accessory distributed across various subspecies drive specific biological functions. Unfortunately, our understanding molecular composition such limited. To begin address this issue, we separated human plasma HDL...

Initial experiments revealed that low concentrations of apolipoprotein (apo) E (0.1 to 5 microg/mL) were effective in inhibiting platelet-derived growth factor (PDGF)-directed smooth muscle cell (SMC) migration by 60% 80%. In contrast, higher apoE, at 25 and 50 microg/mL, necessary achieve similar inhibition PDGF-induced SMC proliferation. The potential role nitric oxide (NO) mediating the inhibitory effects apoE was explored. Results showed that, although 0.1 microg/mL had no effect on NO...

Apolipoprotein J (apoJ), a glycoprotein associated with subclasses of plasma high density lipoproteins (HDL), was found to accumulate in aortic lesions human subject transplantation-associated arteriosclerosis and mice fed high-fat atherogenic diet. Foam cells present mouse valve expressed apoJ mRNA, suggesting local synthesis contributes apoJ's localization atherosclerotic plaque. As prerequisite for elucidating the physiological function by using model, cDNA clones representing homolog...

This research was undertaken to identify the cell surface receptor responsible for mediating apolipoprotein E (apoE) inhibition of platelet-derived growth factor (PDGF)-directed smooth muscle migration. Initial studies revealed expression low density lipoprotein (LDLR), LDL receptor-related protein (LRP), very (VLDL), and apoE receptor-2 in mouse aortic cells. Smooth cells isolated from LDLR-null, VLDL-null, receptor-2-null mice were responsive PDGF-directed migration, suggesting that these...

HDL has been shown to possess a variety of cardio-protective functions, including removal excess cholesterol from the periphery, and inhibition lipoprotein oxidation. It proposed that various subparticles exist, each with distinct protein lipid compositions, which may be responsible for HDL's many functions. We hypothesized functions will co-migrate operational subspecies when separated by gel filtration chromatography. Plasma 10 healthy male donors was fractionated composition phospholipid...

This study showed that synthetic peptides containing either a single copy or tandem repeat of the receptor binding domain sequence apolipoprotein (apo) E, peptide its C-terminal heparin domain, apoE-(211–243), were all effective inhibitors platelet-derived growth factor (PDGF)-stimulated smooth muscle cell proliferation. In contrast, only repeating unit apoE, apoE-(141–155)2, was capable inhibiting PDGF-directed migration. Peptide this sequence, apoE-(141–155), apoE-(211–243) ineffective in...

Pregnancy is accompanied by significant physiological changes, which can impact the health and development of fetus mother. Pregnancy-induced changes in plasma lipoproteins are well documented, with modest to no observed on generic measure high density lipoprotein (HDL) cholesterol. However, pregnancy concentration composition HDL subspecies has not been examined depth. In this prospective study, we collected from 24 nonpregnant 19 pregnant women their second trimester. Using nuclear...

Abstract Objective Weight loss following vertical sleeve gastrectomy (VSG) in youth can range from 10% to 50%. We examined whether there are differences demographic or metabolic parameters before VSG who achieve above‐average weight (AAWL) versus below‐average (BAWL) at 1 year post and if with BAWL still health improvements VSG. Methods Demographic, anthropometric, clinical lab data were collected 1, 3, 6, 12 months after Results Forty‐three a mean age of 16.9 (SD 1.7) years studied; 70%...

High levels of circulating triglycerides (TGs), or hypertriglyceridemia, are key components metabolic diseases, such as type 2 diabetes, syndrome, and CVD. As TGs carried by lipoproteins in plasma, hypertriglyceridemia can result from overproduction lack clearance TG-rich (TRLs) VLDLs. The primary driver TRL is TG hydrolysis mediated LPL. LPL regulated numerous protein components, including the cofactor apolipoprotein C-II, but it not clear how their effects combine to impact across...

High density lipoprotein (HDL) particles are blood-borne complexes whose plasma levels have been associated with protection from cardiovascular disease (CVD). Recent studies demonstrated the existence of distinct HDL subspecies; however, these difficult to isolate and characterize biochemically. Here, we present first report that employs a network-based approach systematically infer subspecies. Healthy human was separated into 58 fractions using our previously published three orthogonal...

The current study compared the effectiveness of various human apolipoprotein E (apoE) isoforms in inhibiting platelet-derived growth factor- (PDGF-) stimulated smooth muscle cell proliferation and migration. incubation primary mouse aortic cells with apoE3 resulted dose-dependent inhibition by 10 ng/mL PDGF. Greater than 50% was observed at 15 μg/mL apoE3. Human apoE2 less effective, requiring a higher concentration to achieve comparable that apoE4 least effective apoE no significant...

Branching morphogenesis of the metanephric kidney is critically dependent on delicate orchestration diverse cellular processes including proliferation, apoptosis, migration, and differentiation. Sphingosine-1-phosphate (S1P) a potent lipid mediator influencing many these events. We report increased expression activity both sphingosine kinases S1P phosphatases during development mouse from induction at embryonic day 11.5 to maturity. Sphingosine kinase exceeded phosphatase in kidneys,...

HDL particles vary in lipidome and proteome, which dictate their individual physicochemical properties, metabolism, biological activities. dysmetabolism nondiabetic hypertriglyceridemia (HTG) involves subnormal HDL-cholesterol apoAI levels. Metabolic anomalies may impact the qualitative features of both proteome. Whether particle content bioactive lipids proteins differentiate subclasses (HDL2b, 2a, 3a, 3b, 3c) HTG is unknown. Moreover, little known effect statin treatment on proteolipidome...

Background The binding of low-density lipoprotein (LDL) to proteoglycans (PGs) in the extracellular matrix (ECM) arterial intima is a key initial step development atherosclerosis. Although many techniques have been developed assess this binding, most methods are labor-intensive and technically challenging standardize across research laboratories. Thus, sensitive, reproducible assay detect LDL PGs needed screen clinical populations for atherosclerosis risk. Objectives aim study was develop...

We sought to develop a new method more efficiently analyze lipid-bound proteins by mass spectrometry using combination of lipid removal agent (LRA) that selectively targets and compatible detergent, anionic acid labile surfactant (AALS), is capable eluting off the LRA. This was compared established methods use alone straight proteomic analysis human plasma after organic solvent delipidation (OSD). Plasma from healthy individuals separated gel filtration chromatography prepared for each...

The endometrium is a dynamic tissue that responds to hormonal cues and growth factors accommodate, regulate, nurture developing embryos. To provide clues about the molecular mechanisms underlying responsiveness of this tissue, we have begun identify genes are expressed at specific stages early pregnancy. One such gene, apolipoprotein I (apoj), encodes secretory glycoprotein capable binding lipids membrane-active proteins. Uterine apoJ gene activity was not detected immediately following...

Background: The entrapment of apolipoprotein (APO) B-100 containing low density lipoproteins (LDL) by proteoglycans (PGs) in the extracellular matrix (ECM) arterial intima is a key initial step development atherosclerotic vascular lesions. High (HDL) can interfere with this process, but underlying mechanism not fully understood and thought to be due APOE. aim study was utilize our recently developed quantitative assay that measures binding LDL PGs ECM investigate how HDL other...

The levels of circulating triglycerides (TG) carried in TG-rich lipoproteins (TGRL) and their remnants are causally associated with cardiovascular disease (CVD). Liberation TG from to peripheral tissues is modulated by TGRL-associated proteins including apolipoproteln A5 (ApoA5), which has been reported profoundly impact metabolism. Present at ~150 ng/ml plasma, it thought work via stimulation (or de-repression) lipoprotein lipase (LPL), hydrolyzes deliver fatty acids cells. To determine...

Lower plasma levels of high‐density lipoproteins (HDL) in adolescents with type 2 diabetes (T2D) have been associated a higher pulse wave velocity (PWV), marker arterial stiffness. Evidence suggests that HDL proteins or particle subspecies are altered T2D and these may drive relationships. In this work, we set out to reveal any specific related stiffness youth from proteomics data. Plasma PWV measurements were previously acquired lean adolescents. Each sample was separated into 18 fractions...

HDL has been shown to possess a variety of cardio-protective functions, including removal excess cholesterol from the periphery, inhibition oxidation, and stimulation endothelial function. It proposed that various sub-particles exist, each with distinct protein lipid compositions. We hypothesized fractionation plasma would separate particles different compositions into populations responsible for functions. Plasma 10 healthy adults was fractionated by gel filtration composition phospholipid...