ArticleProceedings of the National Academy of Sciences of the United States of America2022
A protein of capillary endothelial cells, GPIHBP1, is crucial for plasma triglyceride metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Endothelial Cells as Active Lipid Gatekeepers: Vascular Control of Lipid Handling and Metabolic Homeostasis.Nutrients · 2026Review
- Endothelial Cell Regulation of Lipid Uptake During Feeding and Fasting.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- The Role of Low CD36 Expression in the Development of Non-Small Cell Lung Cancer and Its Potential for Therapy.Cancers · 2026Review
- GPIHBP1 Autoantibody-Related Hypertriglyceridemia in a 12-Year-Old Girl With Systemic Lupus Erythematosus.Case reports in endocrinology · 2026Article
- Mechanosensitive PIEZO2 channels shape coronary artery development.Nature cardiovascular research · 2025Article
- Impact of Selective Peroxisome Proliferator-Activated Receptor (PPAR)-α Modulators and Fibrates on Microvascular Disease: Is There Still Room?Current atherosclerosis reports · 2025Review
- Aspirin impedes non-small cell lung cancer development via fine-tuning the CD36 localization regulated by GPIHBP1.Translational lung cancer research · 2025Article
- Competitive displacement of lipoprotein lipase from heparan sulfate is orchestrated by a disordered acidic cluster in GPIHBP1.Journal of lipid research · 2025Article
- Single-cell RNA sequencing of the carotid artery and femoral artery of rats exposed to hindlimb unloading.Cellular and molecular life sciences : CMLS · 2025Article
- 2025: The year in cardiovascular disease - the year of triglyceride lowering therapies. Can we effectively reduce triglyceride-related residual cardiovascular disease and pancreatitis risk?Archives of medical science : AMS · 2025Article
- From meal to malfunction: exploring molecular pathways, biomarkers and interventions in postprandial cardiometabolic health.Frontiers in cardiovascular medicine · 2025Review
- Increase in GPIHBP1 expression in advanced stage colorectal cancer indicates poor immune surveillance.Translational cancer research · 2024Article
- Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice.The Journal of clinical investigation · 2024Article
- Role of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes.Journal of diabetes investigation · 2023Review
- Intracapillary LPL levels in brown adipose tissue, visualized with an antibody-based approach, are regulated by ANGPTL4 at thermoneutral temperatures.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- QnAs with Stephen G. Young.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
GPIHBP1, a protein of capillary endothelial cells (ECs), is a crucial partner for lipoprotein lipase (LPL) in the lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1, which contains a three-fingered cysteine-rich LU (Ly6/uPAR) domain and an intrinsically disordered acidic domain (AD), captures LPL from within the interstitial spaces (where it is secreted by parenchymal cells) and shuttles it across ECs to the capillary lumen. Without GPIHBP1, LPL remains stranded within the interstitial spaces, causing severe hypertriglyceridemia (chylomicronemia). Biophysical studies revealed that GPIHBP1 stabilizes LPL structure and preserves LPL activity. That discovery was the key to crystallizing the GPIHBP1-LPL complex. The crystal structure revealed that GPIHBP1's LU domain binds, largely by hydrophobic contacts, to LPL's C-terminal lipid-binding domain and that the AD is positioned to project across and interact, by electrostatic forces, with a large basic patch spanning LPL's lipid-binding and catalytic domains. We uncovered three functions for GPIHBP1's AD. First, it accelerates the kinetics of LPL binding. Second, it preserves LPL activity by inhibiting unfolding of LPL's catalytic domain. Third, by sheathing LPL's basic patch, the AD makes it possible for LPL to move across ECs to the capillary lumen. Without the AD, GPIHBP1-bound LPL is trapped by persistent interactions between LPL and negatively charged heparan sulfate proteoglycans (HSPGs) on the abluminal surface of ECs. The AD interrupts the HSPG interactions, freeing LPL-GPIHBP1 complexes to move across ECs to the capillary lumen. GPIHBP1 is medically important;
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.