ArticleCirculation research2009
Vascular-directed tissue factor pathway inhibitor overexpression regulates plasma cholesterol and reduces atherosclerotic plaque development.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
8 citing papers in PubMed, 27 citations in OpenAlex.
- Anti-atherosclerotic effects and molecular targets of salvianolic acids fromFrontiers in pharmacology · 2025Review
- Regulation of coagulation by tissue factor pathway inhibitor: Implications for hemophilia therapy.Journal of thrombosis and haemostasis : JTH · 2022Review
- The contribution of TFPIα to the hemostatic response to injury in mice.Journal of thrombosis and haemostasis : JTH · 2021Article
- Role of tissue factor in atherothrombosis.Current atherosclerosis reports · 2012Review
- Factor VII-activating protease promotes the proteolysis and inhibition of tissue factor pathway inhibitor.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
- Tissue factor pathway inhibitor as a multifunctional mediator of vascular structure.Frontiers in bioscience (Elite edition) · 2012Review
- Tissue factor pathway inhibitor: structure-function.Frontiers in bioscience (Landmark edition) · 2012Review
- Interdependent biological systems, multi-functional molecules: the evolving role of tissue factor pathway inhibitor beyond anti-coagulation.Thrombosis research · 2010Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleTissue factor pathway inhibitor (TFPI) is a potent regulator of the tissue factor pathway and is found in plasma in association with lipoproteins.
objectiveTo determine the role of TFPI in the development of atherosclerosis, we bred mice which overexpress TFPI into the apolipoprotein E-deficient (apoE(-/-)) background. METHODS AND
resultsOn a high-fat diet, smooth muscle 22alpha (SM22alpha)-TFPI/apoE(-/-) mice were shown to have less aortic plaque burden compared to apoE(-/-) mice. Unexpectedly, SM22alpha-TFPI/apoE(-/-) had lower plasma cholesterol levels compared to apoE(-/-) mice. Furthermore, SM22alpha-TFPI mice fed a high-fat diet had lower cholesterol levels than did wild-type mice. Because TFPI is associated with lipoproteins and its carboxyl terminus (TFPIct) has been shown to be a ligand for the very-low-density lipoprotein (VLDL) receptor, we hypothesized that TFPI overexpression may regulate lipoprotein distribution. We quantified VLDL binding and uptake in vitro in mouse aortic smooth muscle cells from SM22alpha-TFPI and wild-type mice. Mouse aortic smooth muscle cells from SM22alpha-TFPI mice demonstrated higher VLDL binding and internalization compared to those from wild-type mice. Because SM22alpha-TFPI mice have increased circulating levels of TFPI antigen, we examined whether TFPIct may act to alter lipoprotein distribution. In vitro, TFPIct increased VLDL binding, uptake, and degradation in murine embryonic fibroblasts. Furthermore, this effect was blocked by heparinase treatment. In vivo, systemic administration of TFPIct reduced plasma cholesterol levels in apoE(-/-) mice.
conclusionsThese studies suggest that overexpression of TFPI lowers plasma cholesterol through the interaction of its carboxyl terminus with lipoproteins and heparan sulfate proteoglycans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.