ArticleJournal of cardiovascular disease research2011
Evaluating the role of connexin43 in congenital heart disease: Screening for mutations in patients with outflow tract anomalies and the analysis of knock-in mouse models.
Article in Journal of cardiovascular disease research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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.
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.
Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- Article
- Injury-induced connexin 43 expression regulates endothelial wound healing.American journal of physiology. Heart and circulatory physiology · 2025Article
- Overexpression of Cx43: Is It an Effective Approach for the Treatment of Cardiovascular Diseases?Biomolecules · 2025Review
- Mutations of theMedicina (Kaunas, Lithuania) · 2024Article
- Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis.Circulation research · 2024Article
- Polygenic Risk Score Improves Cataract Prediction in East Asian Population.Biomedicines · 2022Article
- Connexins and angiogenesis: Functional aspects, pathogenesis, and emerging therapies (Review).International journal of molecular medicine · 2022Review
- Connexin Mutations and Hereditary Diseases.International journal of molecular sciences · 2022Review
- Pericyte Progenitor Coupling to the Emerging Endothelium During Vasculogenesis via Connexin 43.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Spectrum of Genetic Variants in a Cohort of 37 Laterality Defect Cases.Frontiers in genetics · 2022Article
- Connexin43 promotes angiogenesis through activating the HIF-1α/VEGF signaling pathway under chronic cerebral hypoperfusion.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Mechanisms of Connexin Regulating Peptides.International journal of molecular sciences · 2021Review
- VEGFA165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss.JCI insight · 2021Article
- Connexin 43 phosphorylation by casein kinase 1 is essential for the cardioprotection by ischemic preconditioning.Basic research in cardiology · 2021Article
- Article
- Importance of Cx43 for Right Ventricular Function.International journal of molecular sciences · 2021Review
- Genetic Etiology of Left-Sided Obstructive Heart Lesions: A Story in Development.Journal of the American Heart Association · 2021Review
- Phosphorylation of connexin 43 at MAPK, PKC or CK1 sites each distinctly alter the kinetics of epidermal wound repair.Journal of cell science · 2019Article
- Cx43 phosphorylation-mediated effects on ERK and Akt protect against ischemia reperfusion injury and alter the stability of the stress-inducible protein NDRG1.The Journal of biological chemistry · 2019Article
- Targeting MAPK phosphorylation of Connexin43 provides neuroprotection in stroke.The Journal of experimental medicine · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundGJA1 gene encodes a gap junction protein known as connexin 43 (Cx43). Cx43 is abundantly expressed in the ventricular myocardium and in cardiac neural crest cells. Cx43 is proposed to play an important role in human congenital heart disease, as GJA1 knock-out mice die neonatally from outflow tract obstruction. In addition, patients with visceroatrial heterotaxia or hypoplastic left heart syndrome were reported to have point mutations in GJA1 at residues that affect protein kinase phosphorylation and gating of the gap junction channel. However, as these clinical findings were not replicated in subsequent studies, the question remains about the contribution of GJA1 mutations in human congenital heart disease (CHD). MATERIALS AND
methodsWe analyzed the GJA1 coding sequence in 300 patients with CHD from two clinical centers, focusing on outflow tract anomalies. This included 152 with Tetralogy of Fallot from over 200 patients exhibiting outflow tract anomalies, as well as other structural heart defects including atrioventricular septal defects and other valvar anomalies. Our sequencing analysis revealed only two silent nucleotide substitutions in 8 patients. To further assess the possible role of Cx43 in CHD, we also generated two knock-in mouse models with point mutations at serine residues subject to protein kinase C or casein kinase phosphorylation, sites that are known to regulate gating and trafficking of Cx43, respectively.
resultsBoth heterozygous and homozygous knock-in mice were long term viable and did not exhibit overt CHD.
conclusionThe combined clinical and knock-in mouse mutant studies indicate GJA1 mutation is not likely a major contributor to CHD, especially those involving outflow tract anomalies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.