ArticleCirculation. Heart failure2023
Inhibition of Pyk2 Improves Cx43 Intercalated Disc Localization, Infarct Size, and Cardiac Function in Rats With Heart Failure.
Article in Circulation. Heart failure, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 32 citations in OpenAlex.
- Disrupting oncogenic signaling in triple negative breast cancer: The interplay of Cx43, Pyk2, and Src in MDA-MB-231 cells.Cell and tissue research · 2026Article
- Inhibition of Pyk2 prevents Cx43 remodeling and cardiomyocyte injury during hypoxic and adrenergic stress.Journal of molecular and cellular cardiology · 2026Article
- Lycorine Attenuates Cardiac Fibrosis Through the Regulation of PYK2 Expression and Activity.Cardiovascular therapeutics · 2026Article
- Cx45 regulation by kinases and impact of expression in heart failure.Journal of molecular and cellular cardiology · 2025Article
- Translationally controlled tumor protein interacts with connexin 43 and facilitates intercellular coupling between cardiomyocytes.Frontiers in cell and developmental biology · 2025Article
- The PTK2B gene is associated with obesity, adiposity, and leptin levels in children and adolescents.iScience · 2024Article
- Epigenomic biomarkers insights in PBMCs for prognostic assessment of ECMO-treated cardiogenic shock patients.Clinical epigenetics · 2024Article
- Leveraging a neutrophil-derived PCD signature to predict and stratify patients with acute myocardial infarction: from AI prediction to biological interpretation.Journal of translational medicine · 2024Article
- USP38 exacerbates pressure overload-induced left ventricular electrical remodeling.Molecular medicine (Cambridge, Mass.) · 2024Article
- Post translational modifications of connexin 43 in ventricular arrhythmias after myocardial infarction.Molecular biology reports · 2024Review
- Evaluation of Tyrosine Kinase Inhibitors Loaded Injectable Hydrogels for Improving Connexin43 Gap Junction Intercellular Communication.ACS applied materials & interfaces · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHeart failure causes changes in Cx43 (Connexin43) regulation that are associated with arrhythmic heart disease. Pyk2 (proline-rich tyrosine kinase 2) is activated in cardiomyopathies and phosphorylates Cx43 to decrease intercellular communication. This study was designed to determine if Pyk2 inhibition improves cardiac function in a myocardial infarction (MI)-induced heart failure model in rats.
methodsMI (ligation of left anterior descending artery) rats were treated with the Pyk2 inhibitor PF4618433. Hemodynamic and structural parameters were monitored in Sham (n=5), MI-vehicle (n=5), and MI-PF4618433 (n=8) groups. Heart tissues were collected after 6 weeks to assess Pyk2 and Cx43 protein level and localization.
resultsPF4618433 produced no observed adverse effects and inhibited ventricular Pyk2. PF4618433 reduced the MI infarct size from 34% to 17% (
conclusionsUnlike other attempts to decrease Cx43 remodeling after MI-induced heart failure, inhibition of Pyk2 activity maintained Cx43 at the intercalated disc. This may have aided in the reduced infarct size (acute time frame) and improved cardiac function (chronic time frame). Additionally, we provide evidence that Pyk2 is activated following MI in human left ventricle, implicating a novel potential target for therapy in patients with heart failure.
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