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Deletion of newly described pro-survival molecule Pellino-1 increases oxidative stress, downregulates cIAP2/NF-κB cell survival pathway, reduces angiogenic response, and thereby aggravates tissue function in mouse ischemic models.
Selvaraju, Vaithinathan; Thirunavukkarasu, Mahesh; Joshi, Mandip; Oriowo, Babatunde; Shaikh, Inam A; Rishi, Muhammad Tipu; Tapias, Leonidas; Coca-Soliz, Vladimir; Saad, Ibnalwalid; Campbell, Jacob; Pradeep, Seetur R; Swaminathan, Santosh; Yee, Siu-Pok; McFadden, David W; Alexander Palesty, J; Maulik, Nilanjana.
Afiliação
  • Selvaraju V; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut School of Medicine, University of Connecticut Health, Farmington, 06030, CT, USA.
  • Thirunavukkarasu M; Department of Surgery, University of Connecticut Health, 263 Farmington Avenue, Farmington, 06030, CT, USA.
  • Joshi M; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut School of Medicine, University of Connecticut Health, Farmington, 06030, CT, USA.
  • Oriowo B; Department of Surgery, University of Connecticut Health, 263 Farmington Avenue, Farmington, 06030, CT, USA.
  • Shaikh IA; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut School of Medicine, University of Connecticut Health, Farmington, 06030, CT, USA.
  • Rishi MT; Department of Surgery, Saint Mary's Hospital, Waterbury, 06706, CT, USA.
  • Tapias L; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut School of Medicine, University of Connecticut Health, Farmington, 06030, CT, USA.
  • Coca-Soliz V; Department of Surgery, Saint Mary's Hospital, Waterbury, 06706, CT, USA.
  • Saad I; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut School of Medicine, University of Connecticut Health, Farmington, 06030, CT, USA.
  • Campbell J; Department of Surgery, Saint Mary's Hospital, Waterbury, 06706, CT, USA.
  • Pradeep SR; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut School of Medicine, University of Connecticut Health, Farmington, 06030, CT, USA.
  • Swaminathan S; Department of Surgery, Saint Mary's Hospital, Waterbury, 06706, CT, USA.
  • Yee SP; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut School of Medicine, University of Connecticut Health, Farmington, 06030, CT, USA.
  • McFadden DW; Department of Surgery, Saint Mary's Hospital, Waterbury, 06706, CT, USA.
  • Alexander Palesty J; Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut School of Medicine, University of Connecticut Health, Farmington, 06030, CT, USA.
  • Maulik N; Department of Surgery, Saint Mary's Hospital, Waterbury, 06706, CT, USA.
Basic Res Cardiol ; 115(4): 45, 2020 06 14.
Article em En | MEDLINE | ID: mdl-32537701
ABSTRACT

INTRODUCTION:

In the present study, we aimed to explore the functional role of Pellino-1 (Peli1) in inducing neovascularization after myocardial infarction (MI) and hindlimb ischemia (HLI) using Peli1 global knockout mice (Peli1-/-). Recently we have shown that Peli1, an E3 ubiquitin ligase, induce angiogenesis and improve survivability, with decreased necrosis of ischemic skin flaps.

METHODS:

Peli1fl/fl and Peli1-/- mice were subjected to either permanent ligation of the left anterior descending coronary artery (LAD) or sham surgery (S). Tissues from the left ventricular risk area were collected at different time points post-MI. In addition, Peli1fl/fl and Peli1-/- mice were also subjected to permanent ligation of the right femoral artery followed by motor function scores, Doppler analysis for blood perfusion and immunohistochemical analysis.

RESULTS:

Global Peli1 knockout exacerbated myocardial dysfunction, 30 and 60 days after MI compared to wild type (WT) mice as measured by echocardiogram. In addition, Peli1-/- mice also showed decreased motor function scores and perfusion ratios compared with Peli1fl/fl mice 28 days after the induction of HLI. The use of Peli1 in adenoviral gene therapy following HLI in CD1 mice improved the perfusion ratio at 28 days compared to Ad.LacZ-injected mice.

CONCLUSION:

These results suggest new insights into the protective role of Peli1 on ischemic tissues and its influence on survival signaling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Estresse Oxidativo / Neovascularização Fisiológica / Ubiquitina-Proteína Ligases / Isquemia / Infarto do Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Basic Res Cardiol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Estresse Oxidativo / Neovascularização Fisiológica / Ubiquitina-Proteína Ligases / Isquemia / Infarto do Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Basic Res Cardiol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos