Re-evaluation of the anticoagulant properties of high-density lipoprotein-brief report.

Objective: This study was conducted to resolve the striking controversy between our previous report that high-density lipoprotein (HDL) enhances activated protein C (APC)/protein S anticoagulant actions and a subsequent, contradicting report that HDL lacks this activity.

Approach And Results: When fresh HDL preparations from 2 laboratories were subjected to Superose 6 column chromatography, fractions containing HDL-enhanced APC:protein S anticoagulant actions in clotting assays, thereby validating our previous report. Moreover, the ability of HDL to enhance the anticoagulant actions of APC:protein S was neutralized by anti-apoAI antibodies, further indicating that the activity is because of HDL particles and not because of contaminating phospholipid vesicles.

Human oxidation-specific antibodies reduce foam cell formation and atherosclerosis progression.

Objectives: We sought to assess the in vivo importance of scavenger receptor (SR)-mediated uptake of oxidized low-density lipoprotein (OxLDL) in atherogenesis and to test the efficacy of human antibody IK17-Fab or IK17 single-chain Fv fragment (IK17-scFv), which lacks immunologic properties of intact antibodies other than the ability to inhibit uptake of OxLDL by macrophages, to inhibit atherosclerosis.

Background: The unregulated uptake of OxLDL by macrophage SR contributes to foam cell formation, but the importance of this pathway in vivo is uncertain.

Methods: Cholesterol-fed low-density lipoprotein receptor knockout (LDLR(-/-)) mice were treated with intraperitoneal infusion of human IK17-Fab (2.

Screening phosphatidylcholine biomarkers in mouse liver extracts from a hypercholesterolemia study using ESI-MS and chemometrics.

When fed a high-fat, high-cholesterol diet (HFD), homozygous LDL receptor knockout mice exhibit extremely high levels of plasma cholesterol that are expected to influence liver metabolism. One step in the investigation of potential hepatic alterations was the analysis of organic extracts of livers from these and control mice by electrospray mass spectrometry (ESI-MS). Chemometrics (bioinformatics) analysis shows that the sample spectra cluster into two groups: one from mice with plasma cholesterol levels in excess of 900 mg dL(-1) and one from animals with cholesterol levels of 60-250 mg dL(-1).

Estrogen induces lung metastasis through a host compartment-specific response.

Direct proliferative effects of estrogen (E(2)) on estrogen receptor-positive tumors are well documented; however, the potential for E(2) to mediate effects selective for the host (i.e., angiogenesis, vascular permeability, or stromal effects), which influence tumor growth and/or metastasis, has received less attention.

Overexpression of human ApoAI transgene provides long-term atheroprotection in LDL receptor-deficient mice.

The long-term effect of elevated levels of human apolipoprotein AI (apoAI) on atherosclerosis was assessed using human apoAI transgenic mice on a double mutant LDL receptor-deficient (LDLr-/-) and mouse apoAI-deficient (apoAI-/-) background. When they were fed a high fat diet, atherosclerosis in transgenic human apoAI, LDLr-/-, apoAI-/- mice (huapoAITg) was compared with LDLr-/- mice that expressed normal amounts of apoAI (msapoAI) or LDLr-/- mice that lacked mouse apoAI (noapoAI). The atheroprotective effect of human apoAI was demonstrated by a greater than six-fold inhibition in lesion areas in the aortic wall and heart valves compared to the two control strains after 27 or 36 weeks.

Atherosclerotic lesion development in a novel ovary-intact mouse model of perimenopause.

Objective: Since the unexpected results from the Women's Health Initiative, the possible protective role of estrogen in preventing heart disease in perimenopausal and postmenopausal women is uncertain. This study examined atherosclerotic lesion development in ovariectomized versus follicle-depleted ovary-intact cholesterol-fed female low-density lipoprotein (LDL) receptor-deficient mice.

Methods And Results: We studied lesion development in LDL receptor-deficient mice that were ovariectomized or follicle depleted with 4-vinylcyclohexene diepoxide (VCD) to induce ovarian failure, then treated +/- exogenous 17beta-estradiol via pellet implant.

Apolipoprotein A-I is necessary for the in vivo formation of high density lipoprotein competent for scavenger receptor BI-mediated cholesteryl ester-selective uptake.

The severe depletion of cholesteryl ester (CE) in steroidogenic cells of apoA-I(-/-) mice suggests that apolipoprotein (apo) A-I plays a specific role in the high density lipoprotein (HDL) CE-selective uptake process mediated by scavenger receptor BI (SR-BI) in vivo. The nature of this role, however, is unclear because a variety of apolipoproteins bind to SR-BI expressed in transfected cells. In this study the role of apoA-I in SR-BI-mediated HDL CE-selective uptake was tested via analyses of the biochemical properties of apoA-I(-/-) HDL and its interaction with SR-BI on adrenocortical cells, hepatoma cells, and cells expressing a transfected SR-BI.

Hepatic lipase deficiency attenuates mouse ovarian progesterone production leading to decreased ovulation and reduced litter size.

The lipolytic enzyme hepatic lipase (HL) may facilitate mobilization of cholesterol substrate for ovarian steroidogenesis. We investigated whether HL was necessary for optimum reproduction in the female mouse by analyzing breeding performance and ovarian responses to gonadotropins in HL-/- mice. HL-/- female mice bred with HL-/- males had the same pregnancy success rate and pup survival rate as did wild-type (WT) mice but had significantly smaller litters, producing 1.