Evidence map›Paper›PMID 36004642›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2022

Inhibition of the Renin-Angiotensin System Fails to Suppress β-Aminopropionitrile-Induced Thoracic Aortopathy in Mice-Brief Report.

Hisashi Sawada, Satoko Ohno-Urabe, Dien Ye, Michael K Franklin, Jessica J Moorleghen, Deborah A Howatt, Adam E Mullick, Alan Daugherty, Hong S Lu

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.6field-weighted citation impact, top 9% 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, 20 citations in OpenAlex.

  1. Cautionary Data on Antihypertensives in Aortic Diseases.Hypertension (Dallas, Tex. : 1979) · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Sex differences and role of lysyl oxidase-like 2 in angiotensin II-induced hypertension in mice.American journal of physiology. Heart and circulatory physiology · 2024
    Article
  8. Article
  9. Article
  10. Angiotensinogen as a Therapeutic Target for Cardiovascular and Metabolic Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2024
    Review
  11. Lysyl oxidase like-2 in fibrosis and cardiovascular disease.American journal of physiology. Cell physiology · 2023
    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

9 authors at 2 institutions in 1 country.

Hisashi SawadaSaha Cardiovascular Research Center (H.S., S.O.-U., D.Y., M.K.F., J.J.M., D.A.H., A.D., H.S.L.), University of Kentucky, Lexington.ORCID 0000-0003-0017-6236
Satoko Ohno-UrabeSaha Cardiovascular Research Center (H.S., S.O.-U., D.Y., M.K.F., J.J.M., D.A.H., A.D., H.S.L.), University of Kentucky, Lexington.ORCID 0000-0002-4180-2857
Dien YeSaha Cardiovascular Research Center (H.S., S.O.-U., D.Y., M.K.F., J.J.M., D.A.H., A.D., H.S.L.), University of Kentucky, Lexington.ORCID 0000-0002-6433-5032
Michael K FranklinSaha Cardiovascular Research Center (H.S., S.O.-U., D.Y., M.K.F., J.J.M., D.A.H., A.D., H.S.L.), University of Kentucky, Lexington.ORCID 0000-0003-4993-0164
Jessica J MoorleghenSaha Cardiovascular Research Center (H.S., S.O.-U., D.Y., M.K.F., J.J.M., D.A.H., A.D., H.S.L.), University of Kentucky, Lexington.ORCID 0000-0002-2556-6719
Deborah A HowattSaha Cardiovascular Research Center (H.S., S.O.-U., D.Y., M.K.F., J.J.M., D.A.H., A.D., H.S.L.), University of Kentucky, Lexington.ORCID 0000-0002-0078-092X
Adam E MullickIonis Pharmaceuticals, Carlsbad, CA (A.E.M.).ORCID 0000-0003-4600-961X
Alan DaughertySaha Cardiovascular Research Center (H.S., S.O.-U., D.Y., M.K.F., J.J.M., D.A.H., A.D., H.S.L.), University of Kentucky, Lexington.ORCID 0000-0003-2093-3775
Hong S LuSaha Cardiovascular Research Center (H.S., S.O.-U., D.Y., M.K.F., J.J.M., D.A.H., A.D., H.S.L.), University of Kentucky, Lexington.ORCID 0000-0002-0577-2558
University of Kentucky · USIonis Pharmaceuticals (United States) · US

Funding

Determinants of Aorta HeterogeneityR35HL155649 · NHLBI · UNIVERSITY OF KENTUCKY · PI Alan Daugherty · 2021 to 2026
$5.3M
NHLBI NIH HHS R35 HL155649
6 · The paper itself

Abstract

backgroundCross-linking of lysine residues in elastic and collagen fibers is a vital process in aortic development. Inhibition of lysyl oxidase by BAPN (β-aminopropionitrile) leads to thoracic aortopathies in mice. Although the renin-angiotensin system contributes to several types of thoracic aortopathies, it remains unclear whether inhibition of the renin-angiotensin system protects against aortopathy caused by the impairment of elastic fiber/collagen crosslinking.

methodsBAPN (0.5% wt/vol) was started in drinking water to induce aortopathies in male C57BL/6J mice at 4 weeks of age for 4 weeks. Five approaches were used to investigate the impact of the renin-angiotensin system. Bulk RNA sequencing was performed to explore potential molecular mechanisms of BAPN-induced thoracic aortopathies.

resultsLosartan increased plasma renin concentrations significantly, compared with vehicle-infused mice, indicating effective angiotensin II type 1 receptor inhibition. However, losartan did not suppress BAPN-induced aortic rupture and dilatation. Since losartan is a surmountable inhibitor of the renin-angiotensin system, irbesartan, an insurmountable inhibitor, was also tested. Although increased plasma renin concentrations indicated effective inhibition, irbesartan did not ameliorate aortic rupture and dilatation in BAPN-administered mice. Thus, BAPN-induced thoracic aortopathies were refractory to angiotensin II type 1 receptor blockade. Next, we inhibited angiotensin II production by pharmacological or genetic depletion of AGT (angiotensinogen), the unique precursor of angiotensin II. However, neither suppressed BAPN-induced thoracic aortic rupture and dilatation. Aortic RNA sequencing revealed molecular changes during BAPN administration that were distinct from other types of aortopathies in which angiotensin II type 1 receptor inhibition protects against aneurysm formation.

conclusionsInhibition of either angiotensin II action or production of the renin-angiotensin system does not attenuate BAPN-induced thoracic aortopathies in mice.

Indexed as

Aortic Aneurysm, ThoracicAortic RuptureRenin-Angiotensin SystemAminopropionitrileAngiotensin IIAngiotensinogenAnimalsDilatation, PathologicDisease Models, AnimalIrbesartanLosartanLysineMaleMiceMice, Inbred C57BLProtein-Lysine 6-OxidaseAminopropionitrileAngiotensin IIAngiotensinogenIrbesartanLosartanLysineProtein-Lysine 6-OxidaseReceptor, Angiotensin, Type 1Reninangiotensinangiotensinogenaortic aneurysmaortic dissectionBAPNrenin

Identifiers

PMID36004642
PMCPMC9492637
OpenAlexW4293034637

What OpenQuestion holds

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Registered trials

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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.