ArticleNature communications2016
Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- COPI Coatomer Regulates Several Steps of HDL Metabolism.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- A TRAK2-KIF5B complex mediates microtubule-based LDL vesicle transport during endothelial transcytosis.Journal of lipid research · 2026Article
- Early atherogenesis: In search of etiology.International journal of cardiology. Cardiovascular risk and prevention · 2026Review
- Endothelial cannabinoid CB1 receptor deficiency reduces shear stress-induced arterial inflammation and lipid uptake.Nature communications · 2026Article
- GPR182 is a lipoprotein receptor for dietary fat absorption.The Journal of clinical investigation · 2026Article
- The N-terminus of apolipoprotein B mediates the interaction of atherogenic lipoproteins with endothelial cells.The Journal of clinical investigation · 2026Article
- Exercise-Induced Shear Stress, Endothelial Glycocalyx Remodeling, and Atherosclerotic Plaque Stability: A Mechanistic Review.Journal of cardiovascular development and disease · 2026Review
- Kidney-Vascular Metabolic Crosstalk: Altered Lipoproteins in CKD.Circulation research · 2026Review
- The COPI coatomer influences LDL receptor activity, hepatic lipid storage, and apoB secretion.bioRxiv : the preprint server for biology · 2026Article
- Article
- The role of caveolin-1 in atherosclerosis and its molecular mechanism.Lipids in health and disease · 2026Review
- IL-6 triggers lysosomal degradation of LDL-R and enhances LDL-C uptake in vascular endothelial cells via macropinocytosis.Molecular medicine (Cambridge, Mass.) · 2026Article
- Endothelial Cell Regulation of Lipid Uptake During Feeding and Fasting.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- Lipid raft proteomics identify endothelial myosin-9 (MYH9) as a regulator of low-density lipoprotein transcytosis and atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver.Communications biology · 2025Article
- Review
- Review
- Apolipoprotein B-containing lipoproteins in atherogenesis.Nature reviews. Cardiology · 2025Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
Abstract
In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.