Evidence map›Paper›PMID 33097593›Full record

ArticleThe Journal of biological chemistry2020

BMP-9 and LDL crosstalk regulates ALK-1 endocytosis and LDL transcytosis in endothelial cells.

Bo Tao, Jan R Kraehling, Siavash Ghaffari, Cristina M Ramirez, Sungwoon Lee, Joseph W Fowler, Warren L Lee, Carlos Fernandez-Hernando, Anne Eichmann, William C Sessa

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Early atherogenesis: In search of etiology.International journal of cardiology. Cardiovascular risk and prevention · 2026
    Review
  3. Article
  4. Review
  5. Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Transcytosis of LDL Across Arterial Endothelium: Mechanisms and Therapeutic Targets.Arteriosclerosis, thrombosis, and vascular biology · 2025
    Review
  7. Hereditary haemorrhagic telangiectasia.Nature reviews. Disease primers · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Targeting the vasculature in cardiometabolic disease.The Journal of clinical investigation · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Bo TaoDepartment of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA.
Jan R KraehlingDepartment of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA.
Siavash GhaffariDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario Canada.
Cristina M RamirezVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Sungwoon LeeDepartment of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA.
Joseph W FowlerDepartment of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA.
Warren L LeeDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Biochemistry and Medicine, University of Toronto, Toronto, Ontario, Canada.
Carlos Fernandez-HernandoVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Anne EichmannDepartment of Internal Medicine, Cardiovascular Research Center, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA.
William C SessaDepartment of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address: william.sessa@yale.edu.
Yale University · USSt. Michael's Hospital · CAUniversity of Toronto · CA

Funding

Surgery / Physiology CoreP01HL107205 · NHLBI · YALE UNIVERSITY · PI SIMONS, MICHAEL · 2012 to 2022
$18.8M
INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDT32GM007324 · NIGMS · YALE UNIVERSITY · PI BENNETT, ANTON M · 1987 to 2022
$6.2M
Novel insights into the molecular and cellular mechanism regulating lipid metabolism and atherosclerosisR35HL135820 · NHLBI · YALE UNIVERSITY · PI FERNANDEZ HERNANDO, CARLOS · 2017 to 2023
$6.0M
Insights into the Molecular and Cellular Mechanisms governing Endothelial FunctionR35HL139945 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 2018 to 2021
$4.3M
Dual-specificity phosphatase action in muscle diseaseR01AR080152 · NIAMS · YALE UNIVERSITY · PI Anton M Bennett · 2022 to 2026
$2.5M
Role of lipid droplets in insulin resistanceR01DK125492 · NIDDK · YALE UNIVERSITY · PI FERNANDEZ HERNANDO, CARLOS · 2020 to 2023
$1.8M
CIHR PJT-168947NHLBI NIH HHS P01 HL107205NHLBI NIH HHS R35 HL135820NHLBI NIH HHS R35 HL139945NIAMS NIH HHS R01 AR080152NIDDK NIH HHS R01 DK125492NIGMS NIH HHS T32 GM007324
6 · The paper itself

Abstract

Bone morphogenetic protein-9 (BMP-9) is a circulating cytokine that is known to play an essential role in the endothelial homeostasis and the binding of BMP-9 to the receptor activin-like kinase 1 (ALK-1) promotes endothelial cell quiescence. Previously, using an unbiased screen, we identified ALK-1 as a high-capacity receptor for low-density lipoprotein (LDL) in endothelial cells that mediates its transcytosis in a nondegradative manner. Here we examine the crosstalk between BMP-9 and LDL and how it influences their interactions with ALK-1. Treatment of endothelial cells with BMP-9 triggers the extensive endocytosis of ALK-1, and it is mediated by caveolin-1 (CAV-1) and dynamin-2 (DNM2) but not clathrin heavy chain. Knockdown of CAV-1 reduces BMP-9-mediated internalization of ALK-1, BMP-9-dependent signaling and gene expression. Similarly, treatment of endothelial cells with LDL reduces BMP-9-induced SMAD1/5 phosphorylation and gene expression and silencing of CAV-1 and DNM2 diminishes LDL-mediated ALK-1 internalization. Interestingly, BMP-9-mediated ALK-1 internalization strongly re-duces LDL transcytosis to levels seen with ALK-1 deficiency. Thus, BMP-9 levels can control cell surface levels of ALK-1, via CAV-1, to regulate both BMP-9 signaling and LDL transcytosis.

Indexed as

EndocytosisActivin Receptors, Type IICaveolin 1Cell MembraneCells, CulturedEndothelium, VascularGrowth Differentiation Factor 2HumansLipoproteins, LDLPhosphorylationSignal TransductionActivin Receptors, Type IIACVRL1 protein, humanCAV1 protein, humanCaveolin 1GDF2 protein, humanGrowth Differentiation Factor 2Lipoproteins, LDLALK-1cardiovascularcaveolaecaveolinendotheliumLDLlow-density lipoproteinsignalingsignal transductiontranscytosis

Identifiers

PMID33097593
PMCPMC7939458
OpenAlexW3093553483

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.