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Human phospholipid transfer protein (PLTP) mediates the transfer of phospholipids among atheroprotective high-density lipoproteins (HDL) and atherogenic low-density lipoproteins (LDL) by an unknown mechanism. Delineating this mechanism would represent the first step towards understanding PLTP-mediated lipid transfers, which may be important for treating lipoprotein abnormalities and cardiovascular disease. Here, using various electron microscopy techniques, PLTP is revealed to have a banana-shaped structure similar to cholesteryl ester transfer protein (CETP). We provide evidence that PLTP penetrates into the HDL and LDL surfaces, respectively, and then forms a ternary complex with HDL and LDL. Insights into the interaction of PLTP with lipoproteins at the molecular level provide a basis to understand the PLTP-dependent lipid transfer mechanisms for dyslipidemia treatment.

HDL lowers the risk for atherosclerotic cardiovascular disease by promoting cholesterol efflux from macrophage foam cells. However, other antiatherosclerotic properties of HDL are poorly understood. To test the hypothesis that [...]

Introduction: Treatment engagement, adherence, cancellations and other patient-centric data are important predictors of treatment outcome. But often these data are only examined retrospectively. In this investigation, we analysed data from a clinical trial focused on innovative delivery of depression treatment to identify which patients are likely to prefer either in-home or in-person treatment based on pre-treatment characteristics.Methods: Patient satisfaction was assessed in a trial of individuals with depression treated using identical behavioural activation therapy protocols in person or through videoconferencing to the home (N = 87 at post treatment: 42 in-person and 45 in-home participants). The Client Satisfaction Questionnaire was administered at the end of the treatment. A Tobit regression model was used to assess moderation using treatment assignment. Regression lines were generated to model treatment satisfaction as a function of treatment assignment and to identify whether and where the groups intersected. We examined the distributions of the contributing moderators to the subsets of participants above and below the intersection point to identify differences.Results: While no significant differences in patient satisfaction were observed between the two groups, or between patients receiving treatment by different providers, baseline characteristics of the sample could be used to differentiate those with a preference for traditional, in-office care from those preferring in-home care.Discussion: Participants who were more likely to prefer in-home care were characterized by larger proportions of veterans and lower-ranked enlisted service members. They also had more severe symptoms at baseline and less formal education. Understanding client reactions when selecting treatment modality may allow for a more satisfying patient experience. [ABSTRACT FROM AUTHOR]

Background: Phospholipid transfer protein (PLTP) plays an important role in HDL particle metabolism and may modulate hepatic secretion of apolipoprotein B-containing lipoproteins. However, whether PLTP might participate directly in human atherosclerotic lesion formation is unknown., Methods and Results: The cellular and extracellular distributions of PLTP were determined in normal and atherosclerotic human coronary lesions with a monoclonal antibody to human PLTP. Cell types (smooth muscle cells [SMCs] or macrophages), apolipoproteins (apoA-I, apoB, and apoE), and extracellular matrix proteoglycans (biglycan and versican) were identified on adjacent sections with monospecific antibodies. Minimal extracellular PLTP was detected in nonatherosclerotic coronary arteries, but extracellular and cellular PLTP immunostaining was widespread in atherosclerotic lesions. PLTP was detected in foam cell SMCs and in foam cell macrophages, which suggests that cellular cholesterol accumulation might increase PLTP expression in both cell types. This was confirmed by in vitro studies demonstrating that cholesterol loading of macrophages leads to 2- to 3-fold increases in PLTP steady-state mRNA levels, protein expression, and activity. PLTP also was detected in an extracellular distribution, colocalizing with apoA-I, apoB, apoE, and the vascular proteoglycan biglycan. In gel mobility shift assays, both active and inactive recombinant PLTP markedly increased HDL binding to biglycan, which suggests that PLTP may mediate lipoprotein binding to proteoglycans independent of its phospholipid transfer activity., Conclusions: PLTP is present in human atherosclerotic lesions, and its distribution suggests roles for PLTP in both cellular cholesterol metabolism and lipoprotein retention on extracellular matrix.