Novel approaches to determine the functional role of cardiomyocyte specific E3 ligase, Pellino-1 following myocardial infarction.

Autor: Pradeep SR; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA., Thirunavukkarasu M; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA., Accorsi D; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA; Stanley J. Dudrick, Department of Surgery, Saint Mary's Hospital, Waterbury 06706, CT, USA., Swaminathan S; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA; Stanley J. Dudrick, Department of Surgery, Saint Mary's Hospital, Waterbury 06706, CT, USA., Lim ST; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA; Stanley J. Dudrick, Department of Surgery, Saint Mary's Hospital, Waterbury 06706, CT, USA., Cernuda B; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA., Kemerley A; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA., Hubbard J; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA; Stanley J. Dudrick, Department of Surgery, Saint Mary's Hospital, Waterbury 06706, CT, USA., Campbell J; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA., Wilson RL; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA., Coca-Soliz V; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA; Stanley J. Dudrick, Department of Surgery, Saint Mary's Hospital, Waterbury 06706, CT, USA., Tapias L; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA; Stanley J. Dudrick, Department of Surgery, Saint Mary's Hospital, Waterbury 06706, CT, USA., Selvaraju V; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA., Jellison ER; Department of Immunology, University of Connecticut Health, School of Medicine, Farmington, CT, USA., Yee SP; Center for Mouse Genome Modification, University of Connecticut Health, School of Medicine, Farmington, CT, USA., Palesty JA; Stanley J. Dudrick, Department of Surgery, Saint Mary's Hospital, Waterbury 06706, CT, USA., Maulik N; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, School of Medicine, Farmington 06030, CT, USA. Electronic address: nmaulik@uchc.edu.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Jan; Vol. 1870 (1), pp. 166899. Date of Electronic Publication: 2023 Sep 29.
DOI: 10.1016/j.bbadis.2023.166899
Abstrakt: Objectives: Ubiquitination plays a vital role in controlling vascular inflammation, cellular protein quality control, and minimizing misfolded protein toxicity. Pellino-1 (Peli1), a type of E3 ubiquitin ligase, has emerged as a critical regulator of the innate immune response; however, its role in the repair and regeneration of ischemic myocardium remains to be elucidated.
Methods: Mice (8-12 weeks old, male and females) were divided into (i) Wild type (ii) cardiomyocyte-specific Peli1 overexpressed (AMPEL1 Tg/+ ), (iii) cardiomyocyte-specific Peli1 knockout (CP1KO) and were subjected to sham and left anterior descending artery ligation. The tissues were collected at various time points after surgery for Western blot, and immunohistochemical analyses. Echocardiography is performed 30 days after myocardial infarction. Cardiomyocytes isolated from wild-type, Peli1 overexpressed and knockout mice were used to study the interaction between cardiomyocytes and endothelial cells in vitro under oxidative stress and cells were used for Western blot, flow cytometric analysis, and scratch assay.
Results: We observed faster wound closure and increased expression of angiogenic factors with MCECs treated with conditioned media obtained from the AMPEL1 Tg/+ cardiomyocytes compared to CPIKO and WT cardiomyocytes. Again, AMPEL1 Tg/+ MI mice showed preserved systolic function and reduced fibrosis compared to the CPIKOMI and WTMI groups. Capillary and arteriolar density were found to be increased in AMPEL1 Tg/+ MI compared to CP1KOMI. Increased survival and angiogenic factors such as p-Akt, p-MK2, p-IkBα, VEGF, cIAP2, and Bcl2 were observed in AMPEL1 Tg/+ compared to CP1KO and WT mice subjected to MI.
Conclusion: The present study uncovers the crucial role of cardiac Peli1 as a regulator of the repair and regeneration of ischemic myocardium by using multiple genetically engineered mouse models.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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