Evidence map›Paper›PMID 39827863›Full record

ArticleJournal of vascular research2025

Fibrillin-1 Deficiency Perturbs Aortic Cholinergic Relaxation and Adrenergic Contraction in a Mouse Model of Early Onset Progressively Severe Marfan Syndrome.

Anna Cantalupo, Keiichi Asano, Sergey Dikalov, Dylan Gordon, Francesco Ramirez

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of vascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Integrin Signaling Pathways in Aortic Aneurysm and Dissection.Reviews in cardiovascular medicine · 2026
    Review
  3. Article
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

5 authors.

Anna CantalupoDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Keiichi AsanoDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Sergey DikalovDivision of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Dylan GordonDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Francesco RamirezDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Funding

TGFB-Dependent Mechanoresponses by Aortic Smooth Muscle Cells Govern AneurysmsP01HL134605 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HUMPHREY, JAY D. · 2018 to 2022
$12.1M
Sirtuin 3 Inactivation and SOD2 Acetylation in Vascular Dysfunction and HypertensionR01HL157583 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DIKALOV, SERGEY · 2021 to 2024
$2.4M
Targeting Mitochondrial Cyclophilin D in Vascular Oxidative Stress and HypertensionR01HL144943 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DIKALOV, SERGEY · 2019 to 2022
$1.7M
NHLBI NIH HHS P01 HL134605NHLBI NIH HHS R01 HL144943NHLBI NIH HHS R01 HL157583
6 · The paper itself

Abstract

introductionThe pathogenic role of nitric oxide (NO) signaling during development of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is currently unclear. We characterized vasomotor function and its relationship to the activity of the NO-generating enzymes in mice with early onset progressively severe MFS.

methodsWire myography, immunoblotting, measurements of aortic NO, and superoxide levels were used to compare vasomotor function, contractile protein levels, and the activity of endothelial and inducible NO synthase (eNOS and iNOS, respectively) in ascending thoracic aortas of Fbn1mgR/mgR mice relative to wild-type littermates.

resultsIsometric force measurements of aortic rings from 16-day-old male Fbn1mgR/mgR mice revealed a significant reduction in acetylcholine-induced relaxation and increased phenylephrine (PE)-promoted contractility, associated with abnormally low eNOSSer1177 phosphorylation, decreased NO production, and augmented superoxide levels. Greater aortic contractility was associated with α1-adrenoceptor upregulation and normal levels of contractile proteins. While iNOS inhibition had no effect on vasomotor functions, mutant aortic rings preincubated with a nonspecific NOS inhibitor yielded a greater PE response, implying a significant contribution of endothelial dysfunction to aortic hypercontractility.

conclusionImpaired eNOS signaling disrupts aortic cholinergic relaxation and adrenergic contraction in MFS mice with dissecting TAA.

introductionThe pathogenic role of nitric oxide (NO) signaling during development of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is currently unclear. We characterized vasomotor function and its relationship to the activity of the NO-generating enzymes in mice with early onset progressively severe MFS.

methodsWire myography, immunoblotting, measurements of aortic NO, and superoxide levels were used to compare vasomotor function, contractile protein levels, and the activity of endothelial and inducible NO synthase (eNOS and iNOS, respectively) in ascending thoracic aortas of Fbn1mgR/mgR mice relative to wild-type littermates.

resultsIsometric force measurements of aortic rings from 16-day-old male Fbn1mgR/mgR mice revealed a significant reduction in acetylcholine-induced relaxation and increased phenylephrine (PE)-promoted contractility, associated with abnormally low eNOSSer1177 phosphorylation, decreased NO production, and augmented superoxide levels. Greater aortic contractility was associated with α1-adrenoceptor upregulation and normal levels of contractile proteins. While iNOS inhibition had no effect on vasomotor functions, mutant aortic rings preincubated with a nonspecific NOS inhibitor yielded a greater PE response, implying a significant contribution of endothelial dysfunction to aortic hypercontractility.

conclusionImpaired eNOS signaling disrupts aortic cholinergic relaxation and adrenergic contraction in MFS mice with dissecting TAA.

Indexed as

Aorta, ThoracicAortic Aneurysm, ThoracicFibrillin-1Marfan SyndromeAcetylcholineAdipokinesAnimalsDisease Models, AnimalEndothelium, VascularMaleMiceMice, Inbred C57BLMice, TransgenicMuscle RelaxationMutationMyographyAcetylcholineAdipokinesFbn1 protein, mouseFibrillin-1Nitric OxideNitric Oxide Synthase Type IINitric Oxide Synthase Type IIISuperoxidesEndothelial dysfunctionEndothelial nitric oxide synthaseMarfan syndromeThoracic aortic aneurysm and dissectionVasomotor function

Identifiers

PMID39827863
PMCPMC11961321

What Socratic holds

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LicenceCC BY-NC
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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 Socratic graph.