Evidence map›Paper›PMID 35460403›Full record

ArticleEuropean journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery2022

Layer-specific Nos3 expression and genotypic distribution in bicuspid aortic valve aortopathy.

Jennifer C Hill, Marie Billaud, Tara D Richards, Mary P Kotlarczyk, Sruti Shiva, Julie A Phillippi, Thomas G Gleason

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Article in European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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4citing papers in PubMed
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3 · Its place in the literature

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4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Jennifer C HillDepartment of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Marie BillaudDepartment of Surgery, Division of Thoracic and Cardiac Surgery, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-7591-0362
Tara D RichardsDepartment of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-5830-239X
Mary P KotlarczykDepartment of Medicine, Division of Geriatric Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Sruti ShivaDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Julie A PhillippiDepartment of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-9879-2039
Thomas G GleasonDepartment of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-5858-6073

Funding

ROS Mechanisms in BAV AortopathyR01HL109132 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GLEASON, THOMAS GILLETTE · 2012 to 2024
$6.2M
Matrix mediated vasa vasorum dysfunction in thoracic aortic diseaseR01HL131632 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PHILLIPPI, JULIE A · 2017 to 2021
$1.9M
NHLBI NIH HHS R01 HL109132NHLBI NIH HHS R01 HL131632
6 · The paper itself

Abstract

objectivesWe hypothesized that expression and activity of nitric oxide synthase-3 enzyme (Nos3) in bicuspid aortic valve (BAV) aortopathy are related to tissue layer and Nos3 genotype.

methodsGene expression of Nos3 and platelet and endothelial cell adhesion molecule-1 (Pecam1) and NOS activity were measured in intima-containing media and adventitial specimens of ascending aortic tissue. The presence of 2 Nos3 single-nucleotide polymorphisms (SNPs; -786T/C and 894G/T) was determined for non-aneurysmal (NA) and aneurysmal patients with BAV (n = 40, 89, respectively); patients with tricuspid aortic valve (TAV) and aneurysm (n = 151); and NA patients with TAV (n = 100).

resultsElevated Nos3 relative to Pecam1 and reduced Pecam1 relative to a housekeeping gene were observed within intima-containing aortic specimens from BAV patients when compared with TAV patients. Lower Nos3 in the adventitia of aneurysmal specimens was noted when compared with specimens of NA aorta, independent of valve morphology. NOS activity was similar among cohorts in media/intima and decreased in the diseased adventitia, relative to control patients. Aneurysmal BAV patients exhibited an under-representation of the wild-type genotype for -786 SNP. No differences in genotype distribution were noted for 894 SNP. Primary intimal endothelial cells from patients with at least 1 C allele at -786 SNP exhibited lower Nos3 when compared with wild-type cells.

conclusionsThese findings of differential Nos3 in media/intima versus adventitia depending on valve morphology or aneurysm reveal new information regarding aneurysmal pathophysiology and support our ongoing assertion that there are distinct mechanisms giving rise to ascending aortopathy in BAV and TAV patients.

Indexed as

Bicuspid Aortic Valve DiseaseHeart Valve DiseasesAortic ValveEndothelial CellsGenotypeHumansNitric Oxide Synthase Type IIINitric Oxide Synthase Type IIINOS3 protein, humanAneurysmBicuspid aortic valveEndothelial cellsNitric oxide synthase 3Single-nucleotide polymorphism

Identifiers

PMID35460403
PMCPMC9615433

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