Evidence map›Paper›PMID 39835393›Full record

ArticleCirculation research2025

Non-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease.

Rolando A Cuevas, Luis Hortells, Claire C Chu, Ryan Wong, Alex Crane, Camille K Boufford, Cailyn Regan, William J Moorhead, Michael J Bashline, Aneesha Parwal and 10 more

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In one paragraph

Article in Circulation research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
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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

20 authors.

Rolando A CuevasDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).ORCID 0000-0002-3571-5845
Luis HortellsCardiovascular Research Group, Department of Medical Biology, Faculty of Health Science, UiT-The Arctic University of Norway, 9019 Tromsø, Norway (L.H.).
Claire C ChuDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).ORCID 0000-0002-1735-5137
Ryan WongDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).ORCID 0000-0002-1251-758X
Alex CraneDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).
Camille K BouffordDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).ORCID 0000-0003-1019-9431
Cailyn ReganDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).
William J MoorheadDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).
Michael J BashlineDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).ORCID 0000-0001-6686-8978
Aneesha ParwalDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).ORCID 0000-0003-4256-9345
Angelina M PariseDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).ORCID 0000-0003-0207-2510
Parya BehzadiDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).ORCID 0000-0002-3807-1109
Mark J BrownDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).ORCID 0000-0002-3874-1352
Aditi U GurkarAging Institute, Division of Geriatrics, Department of Medicine, University of Pittsburgh, Pittsburgh, PA (A.U.G.).ORCID 0000-0003-4338-0624
Dennis BruemmerDepartment of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH (D.B.).
John SembratDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA (J.S.).ORCID 0000-0003-4108-803X
Ibrahim SultanDivision of Cardiac Surgery, Department of Cardiothoracic Surgery, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA (I.S., T.G.G.).ORCID 0000-0002-1737-4012
Thomas G GleasonDivision of Cardiac Surgery, Department of Cardiothoracic Surgery, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA (I.S., T.G.G.).ORCID 0000-0001-5858-6073
Marie BillaudDepartment of Surgery, Division of Cardiac Surgery, Brigham and Women's Hospital & Harvard Medical School, Boston, MA (M.B.).ORCID 0000-0002-7591-0362
Cynthia St HilaireDivision of Cardiology, Department of Medicine, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA (R.A.C., C.C.C., R.W., A.C., C.K.B., C.R., W.J.M., M.J. Bashline, A.P., A.M.P., P.B., M.J.B., C.S.H.).ORCID 0000-0003-1871-6915

Funding

The Role of Telomerase in Calcific Aortic Valve DiseaseR01HL142932 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ST. HILAIRE, CYNTHIA · 2018 to 2022
$2.3M
Telomere dysfunction driven molecular outputs in the cardiac unitR01ES035733 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Aditi U Gurkar · 2024 to 2026
$1.7M
Telomerase Reverse Transcriptase in Aortic Valve CalcificationR56HL168657 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ST. HILAIRE, CYNTHIA · 2024 to 2024
$750k
American Heart Association-American Stroke Association 902641NHLBI NIH HHS R01 HL142932NHLBI NIH HHS R56 HL168657NIEHS NIH HHS R01 ES035733
6 · The paper itself

Abstract

backgroundCalcific aortic valve disease is the pathological remodeling of valve leaflets. The initial steps in valve leaflet osteogenic reprogramming are not fully understood. As TERT (telomerase reverse transcriptase) overexpression primes mesenchymal stem cells to differentiate into osteoblasts, we investigated whether TERT contributes to the osteogenic reprogramming of valve interstitial cells.

methodsHuman control and calcific aortic valve disease aortic valve leaflets and patient-specific human aortic valve interstitial cells were used in in vivo and in vitro calcification assays. Loss of function experiments in human aortic valve interstitial cells and cells isolated from

resultsTERT protein was highly expressed in calcified valve leaflets without changes in telomere length, DNA damage, or senescence markers, and these features were retained in isolated primary human aortic valve interstitial cells.

conclusionsTERT's non-canonical activity is required to initiate calcification. TERT is upregulated via inflammatory signaling pathways and partners with STAT5 to bind the RUNX2 gene promoter. These data identify a novel mechanism and potential therapeutic target to decrease vascular calcification.

Indexed as

Aortic ValveAortic Valve StenosisCalcinosisOsteogenesisTelomeraseAnimalsCells, CulturedCore Binding Factor Alpha 1 SubunitFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutCore Binding Factor Alpha 1 SubunitTelomeraseTERT protein, humanTert protein, mouseaortic valveinflammationosteogenesisvascular calcification

Identifiers

PMID39835393
PMCPMC11825275

What Socratic holds

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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.