Article in Circulation. Heart failure, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
0numbers the graph read from it
0cells of the map it votes in
2citing 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.
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
19 authors.
Jing ZhangDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.ORCID 0000-0002-5871-4490
Fabian ZanellaDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.ORCID 0000-0001-6985-4221
Matthew W EllisDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.ORCID 0000-0002-7407-4374
William H BradfordDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.
Erika Joana Gutierrez-LaraDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.ORCID 0000-0003-1780-7487
Tsui-Min WangDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.ORCID 0000-0002-0788-6065
Kyohei FujitaDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.ORCID 0000-0001-8724-3096
Charlize DuronDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.
Ioannis KarakikesSchool of Medicine, Stanford Cardiovascular Institute, Stanford University, Palo Alto, CA (I.K.).ORCID 0000-0002-4348-600X
Robert C LyonDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.
Valeria MezzanoDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.ORCID 0000-0003-4675-9146
Jason D RobertsPopulation Health Research Institute, Hamilton Health Sciences, McMaster University, ON, Canada (J.D.R.).ORCID 0000-0003-0268-6723
Cassiano CarromeuDepartments of Pediatrics/Cellular and Molecular Medicine (C.C., A.R.M.), University of California San Diego, La Jolla.
Yusu GuDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.ORCID 0000-0002-9543-8472
Jody L MartinDepartment of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois, Chicago (J.L.M.).ORCID 0000-0001-5607-3338
Alysson R MuotriDepartments of Pediatrics/Cellular and Molecular Medicine (C.C., A.R.M.), University of California San Diego, La Jolla.ORCID 0000-0003-0867-2875
Melvin M ScheinmanCardiac Electrophysiology Section, University of California San Francisco (M.M.S.).ORCID 0000-0001-6295-3753
Kirk L PetersonDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.ORCID 0000-0001-9042-5763
Farah SheikhDepartment of Medicine (J.Z., F.Z., M.W.E., W.H.B., E.J.G.-L., T.-M.W., K.F., C.D., R.C.L., V.M., Y.G., K.L.P., F.S.), University of California San Diego, La Jolla.ORCID 0000-0003-2610-0125
Funding
VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
UCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Uncovering Molecular Targets for Arrhythmogenic Cardiomyopathy TherapeuticsR01HL162369 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHEIKH, FARAH · 2022 to 2025
$2.0M
Understanding Early Drivers and Therapeutic Targets for Severe Forms of Arrhythmogenic CardiomyopathyR01HL181001 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Farah Sheikh · 2025 to 2026
$1.4M
JEOL JEM-1400Plus Transmission Electron MicroscopeS10OD023527 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FARQUHAR, MARILYN GIST · 2017 to 2017
$579k
Characterizing regulatory mechanisms of desmosomal protein expression in arrhythmogenic cardiomyopathyF32HL172624 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELLIS, MATTHEW W · 2024 to 2025
backgroundArrhythmogenic cardiomyopathy (ACM) is a fatal genetic heart disease primarily caused by mutations in desmosomal genes, leading to impaired cell-cell adhesion, ventricular arrhythmias, and progressive heart failure. Although gene therapy for specific ACM populations shows promise, it remains unclear whether mutation-agnostic pathways dysregulated across desmosomal mutations could be exploited for therapeutic intervention in this genetically broad and severe population. The reduction in expression of the ventricular gap junction protein Cx43 (connexin-43) is a common molecular alteration underlying desmosomal junctional deficits and arrhythmias, suggesting a potential common underlying mechanism and a therapeutic target for ACM. We hypothesized that restoration of Cx43 expression could be a mutation-agnostic intervention for ACM.
methodsWe exploited adeno-associated-viral-mediated gene therapy to restore the gap junction protein, Cx43, in genetic mouse models and human stem cell models of ACM, harboring loss or mutations in desmosomal genes, including
resultsAdministration of AAV-Cx43 (adeno-associated-viral-mediated connexin-43) gene therapy alleviated the severe biventricular dilatation, contractile dysfunction, and arrhythmias, while prolonging lifespan in 2 severe desmosomal ACM mouse models, either harboring
conclusionsBy using mouse and human models of desmosomal ACM harboring different mutational backgrounds, we show the sufficiency of Cx43 gene therapy and its restoration to modify and alleviate ACM deficits. These data suggest that noncanonical functions of Cx43, including mechanical modulation and reassembly of the desmosome, are a therapeutic target with the potential to treat diverse ACM populations.
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.
Connexin-43 Restoration Alleviates Desmosomal Arrhythmogenic Cardiomyopathy. · full record | OpenQuestion