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- Title
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.
- Authors
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
- 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.
- Subjects
UBIQUITIN ligases; OXIDATIVE stress; FEMORAL artery; KNOCKOUT mice; BLOOD testing; TALL-1 (Protein)
- Publication
Basic Research in Cardiology, 2020, Vol 115, Issue 4, p1
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-020-0804-4