Evidence map›Paper›PMID 36172868›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2022

Aortic Cellular Diversity and Quantitative Genome-Wide Association Study Trait Prioritization Through Single-Nuclear RNA Sequencing of the Aneurysmal Human Aorta.

Elizabeth L Chou, Mark Chaffin, Bridget Simonson, James P Pirruccello, Amer-Denis Akkad, Mahan Nekoui, Christian Lacks Lino Cardenas, Kenneth C Bedi, Craig Nash, Dejan Juric and 6 more

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 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
6.5field-weighted citation impact, top 2% 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

35 citing papers in PubMed, 46 citations in OpenAlex.

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  9. Single-cell Profiling Reveals Cooperative Participation ofInternational journal of medical sciences · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 1 country.

Elizabeth L Chou *Division of Vascular and Endovascular Surgery (E.L.C.), Massachusetts General Hospital, Boston.ORCID 0000-0002-0997-6785
Mark Chaffin *Cardiovascular Disease Initiative (E.L.C., M.C., B.S., J.P.P., M.N., C.N., P.T.E., M.E.L.), Broad Institute, Cambridge, MA.ORCID 0000-0002-1234-5562
Bridget Simonson *Cardiovascular Disease Initiative (E.L.C., M.C., B.S., J.P.P., M.N., C.N., P.T.E., M.E.L.), Broad Institute, Cambridge, MA.
James P PirruccelloCardiology Division (J.P.P., C.L.L.C., E.M.I., P.T.E., M.E.L.), Massachusetts General Hospital, Boston.ORCID 0000-0001-6088-4037
Amer-Denis AkkadPrecision Cardiology Laboratory, Bayer US LLC, Cambridge, MA (A.-D.A., C.K.).
Mahan NekouiDemoulas Center for Cardiac Arrhythmias (J.P.P., M.N., P.T.E.), Massachusetts General Hospital, Boston.ORCID 0000-0001-7466-4801
Christian Lacks Lino CardenasCardiology Division (J.P.P., C.L.L.C., E.M.I., P.T.E., M.E.L.), Massachusetts General Hospital, Boston.ORCID 0000-0001-5491-4375
Kenneth C BediPerelman School of Medicine, University of Pennsylvania, Philadelphia (K.C.B., K.B.M.).ORCID 0000-0003-3588-9324
Craig NashCardiovascular Disease Initiative (E.L.C., M.C., B.S., J.P.P., M.N., C.N., P.T.E., M.E.L.), Broad Institute, Cambridge, MA.
Dejan JuricCancer Center (D.J.), Massachusetts General Hospital, Boston.
James R StoneDepartment of Pathology (J.R.S.), Massachusetts General Hospital, Boston.
Eric M IsselbacherCardiology Division (J.P.P., C.L.L.C., E.M.I., P.T.E., M.E.L.), Massachusetts General Hospital, Boston.
Kenneth B MarguliesPerelman School of Medicine, University of Pennsylvania, Philadelphia (K.C.B., K.B.M.).ORCID 0000-0002-8093-4465
Carla KlattenhoffPrecision Cardiology Laboratory, Bayer US LLC, Cambridge, MA (A.-D.A., C.K.).
Patrick T EllinorCardiology Division (J.P.P., C.L.L.C., E.M.I., P.T.E., M.E.L.), Massachusetts General Hospital, Boston.ORCID 0000-0002-2067-0533
Mark E LindsayDivision of Vascular and Endovascular Surgery (E.L.C.), Massachusetts General Hospital, Boston.ORCID 0000-0001-6724-7938
Cardiovascular Institute of the South · USMassachusetts General Hospital · USBroad Institute · USUniversity of Pennsylvania · USBayer (United States) · USPrecision for Medicine (United States) · US

Funding

IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
MULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1M
Integrative genomics of human heart failureR01HL105993 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ASHLEY, EUAN A, CAPPOLA, THOMAS P. · 2011 to 2014
$8.9M
Using Electrocardiogram Genetics to Inform Arrhythmia RiskR01HL157635 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS, MIRSHAHI, TOORAJ · 2022 to 2025
$2.9M
The Role of HDAC9/MITR in the Pathogenesis of Thoracic Aortic Aneurysm (TAA)R01HL130113 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI LINDSAY, MARK E · 2016 to 2020
$2.0M
Mentoring in Arrhythmia ResearchK24HL105780 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2011 to 2020
$1.2M
Deep learning to enable the genetic analysis of aortaK08HL159346 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PIRRUCCELLO, JAMES · 2021 to 2025
$827k
Novel molecular mechanisms of vascular smooth muscle cell-mediated large and small artery calcificationK01HL164687 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Christian Lacks Lino Cardenas · 2022 to 2026
$808k
Targeting Chronic Senescence to Restore Tissue Homeostasis in Myhre syndromeR21AR080778 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI LINDSAY, MARK E, MOU, HONGMEI · 2022 to 2023
$386k
NHLBI NIH HHS K01 HL164687NHLBI NIH HHS K08 HL159346NHLBI NIH HHS K24 HL105780NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL105993NHLBI NIH HHS R01 HL130113NHLBI NIH HHS R01 HL157635NHLBI NIH HHS T32 HL007208NIAMS NIH HHS R21 AR080778
6 · The paper itself

Abstract

backgroundMural cells in ascending aortic aneurysms undergo phenotypic changes that promote extracellular matrix destruction and structural weakening. To explore this biology, we analyzed the transcriptional features of thoracic aortic tissue.

methodsSingle-nuclear RNA sequencing was performed on 13 samples from human donors, 6 with thoracic aortic aneurysm, and 7 without aneurysm. Individual transcriptomes were then clustered based on transcriptional profiles. Clusters were used for between-disease differential gene expression analyses, subcluster analysis, and analyzed for intersection with genetic aortic trait data.

resultsWe sequenced 71 689 nuclei from human thoracic aortas and identified 14 clusters, aligning with 11 cell types, predominantly vascular smooth muscle cells (VSMCs) consistent with aortic histology. With unbiased methodology, we found 7 vascular smooth muscle cell and 6 fibroblast subclusters. Differentially expressed genes analysis revealed a vascular smooth muscle cell group accounting for the majority of differential gene expression. Fibroblast populations in aneurysm exhibit distinct behavior with almost complete disappearance of quiescent fibroblasts. Differentially expressed genes were used to prioritize genes at aortic diameter and distensibility genome-wide association study loci highlighting the genes

conclusionsUsing nuclear RNA sequencing, we describe the cellular diversity of healthy and aneurysmal human ascending aorta. Sporadic aortic aneurysm is characterized by differential gene expression within known cellular classes rather than by the appearance of novel cellular forms. Single-nuclear RNA sequencing of aortic tissue can be used to prioritize genes at aortic trait loci.

Indexed as

Aortic AneurysmAortic Aneurysm, ThoracicActininAortaGenome-Wide Association StudyHumansMuscle, Smooth, VascularMyocytes, Smooth MuscleRNA, NuclearSequence Analysis, RNATransforming Growth Factor betaActininRNA, NuclearTransforming Growth Factor betaaortic aneurysmsextracellular matrixfibroblastgenome-wide association studythoracictranscriptomes

Identifiers

PMID36172868
PMCPMC9613617
OpenAlexW4297965604

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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.