Evidence map›Paper›PMID 36472907›Full record

ArticleJCI insight2023

LRP1 protects against excessive superior mesenteric artery remodeling by modulating angiotensin II-mediated signaling.

Jackie M Zhang, Dianaly T Au, Hisashi Sawada, Michael K Franklin, Jessica J Moorleghen, Deborah A Howatt, Pengjun Wang, Brittany O Aicher, Brian Hampton, Mary Migliorini and 8 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 27% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Angiotensin II Induces Abdominal Aortic Branch Aneurysms inArteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Circulation research · 2024
    Article
  10. Review
  11. Angiotensinogen as a Therapeutic Target for Cardiovascular and Metabolic Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2024
    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

18 authors at 5 institutions in 2 countries.

Jackie M ZhangCenter for Vascular and Inflammatory Diseases and.
Dianaly T AuCenter for Vascular and Inflammatory Diseases and.
Hisashi SawadaSaha Cardiovascular Research Center and Saha Aortic Center and.
Michael K FranklinSaha Cardiovascular Research Center and Saha Aortic Center and.
Jessica J MoorleghenSaha Cardiovascular Research Center and Saha Aortic Center and.
Deborah A HowattSaha Cardiovascular Research Center and Saha Aortic Center and.
Pengjun WangSaha Cardiovascular Research Center and Saha Aortic Center and.
Brittany O AicherCenter for Vascular and Inflammatory Diseases and.
Brian HamptonCenter for Vascular and Inflammatory Diseases and.
Mary MiglioriniCenter for Vascular and Inflammatory Diseases and.
Fenge NiCenter for Vascular and Inflammatory Diseases and.
Adam E MullickIonis Pharmaceuticals, Carlsbad, California, USA.
Mashhood M WaniCenter for Vascular and Inflammatory Diseases and.
Areck A UcuzianCenter for Vascular and Inflammatory Diseases and.
Hong S LuSaha Cardiovascular Research Center and Saha Aortic Center and.
Selen C MuratogluCenter for Vascular and Inflammatory Diseases and.
Alan DaughertySaha Cardiovascular Research Center and Saha Aortic Center and.
Dudley K StricklandCenter for Vascular and Inflammatory Diseases and.
Center for Vascular Biology Research · USCardiovascular Research Center · BRUniversity of Maryland, Baltimore · USUniversity of Kentucky · USIonis Pharmaceuticals (United States) · US

Funding

Vascular Biology Training ProgramT32HL007698 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI Rosemary A Kozar, Dudley K. Strickland · 1991 to 2026
$8.7M
Role of LDL receptor family members in protecting the vasculatureR35HL135743 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI STRICKLAND, DUDLEY K. · 2017 to 2023
$5.4M
Determinants of Aorta HeterogeneityR35HL155649 · NHLBI · UNIVERSITY OF KENTUCKY · PI Alan Daugherty · 2021 to 2026
$5.3M
Mechanisms of aortopathy in LRP1 deficiencyK08HL146893 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI UCUZIAN, ARECK A · 2020 to 2024
$816k
Role of LRP1 in Angiotensin Signaling and Vascular RemodelingF31HL131293 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI AU, DIANALY THI · 2016 to 2017
$59k
NHLBI NIH HHS F31 HL131293NHLBI NIH HHS K08 HL146893NHLBI NIH HHS R35 HL135743NHLBI NIH HHS R35 HL155649NHLBI NIH HHS T32 HL007698
6 · The paper itself

Abstract

Vascular smooth muscle cells (vSMCs) exert a critical role in sensing and maintaining vascular integrity. These cells abundantly express the low-density lipoprotein receptor-related protein 1 (LRP1), a large endocytic signaling receptor that recognizes numerous ligands, including apolipoprotein E-rich lipoproteins, proteases, and protease-inhibitor complexes. We observed the spontaneous formation of aneurysms in the superior mesenteric artery (SMA) of both male and female mice in which LRP1 was genetically deleted in vSMCs (smLRP1-/- mice). Quantitative proteomics revealed elevated abundance of several proteins in smLRP1-/- mice that are known to be induced by angiotensin II-mediated (AngII-mediated) signaling, suggesting that this pathway was dysregulated. Administration of losartan, an AngII type I receptor antagonist, or an angiotensinogen antisense oligonucleotide to reduce plasma angiotensinogen concentrations restored the normal SMA phenotype in smLRP1-/- mice and prevented aneurysm formation. Additionally, using a vascular injury model, we noted excessive vascular remodeling and neointima formation in smLRP1-/- mice that was restored by losartan administration. Together, these findings reveal that LRP1 regulates vascular integrity and remodeling of the SMA by attenuating excessive AngII-mediated signaling.

Indexed as

Angiotensin IIMesenteric Artery, SuperiorAngiotensinogenAnimalsFemaleLosartanLow Density Lipoprotein Receptor-Related Protein-1MaleMiceSignal TransductionAngiotensin IIAngiotensinogenLosartanLow Density Lipoprotein Receptor-Related Protein-1Lrp1 protein, mouseCardiovascular diseaseVascular Biology

Identifiers

PMID36472907
PMCPMC9977308
OpenAlexW4310778441

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.