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

被引：14

作者：

Selvaraju, Vaithinathan ^{[1
,2
]}

Thirunavukkarasu, Mahesh ^{[1
,2
]}

Joshi, Mandip ^{[1
,3
]}

Oriowo, Babatunde ^{[1
,3
]}

Shaikh, Inam A. ^{[1
,3
]}

Rishi, Muhammad Tipu ^{[1
,3
]}

Tapias, Leonidas ^{[1
,3
]}

Coca-Soliz, Vladimir ^{[1
,3
]}

Saad, Ibnalwalid ^{[1
,3
]}

Campbell, Jacob ^{[1
,2
]}

Pradeep, Seetur R. ^{[1
,2
]}

Swaminathan, Santosh ^{[1
,3
]}

Yee, Siu-Pok ^{[4
]}

McFadden, David W. ^{[2
]}

Palesty, J. Alexander ^{[3
]}

Maulik, Nilanjana ^{[1
,2
]}

机构：

[1] Univ Connecticut, Univ Connecticut Hlth, Dept Surg, Mol Cardiol & Angiogenesis Lab,Sch Med, Farmington, CT 06030 USA

[2] Univ Connecticut Hlth, Dept Surg, 263 Farmington Ave, Farmington, CT 06030 USA

[3] St Marys Hosp, Dept Surg, Waterbury, CT 06706 USA

[4] Univ Connecticut Hlth, Ctr Mouse Genome Modificat, Farmington, CT USA

来源：

BASIC RESEARCH IN CARDIOLOGY | 2020年 / 115卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Myocardial infarction; cIAP2; Hindlimb ischemia; Angiogenesis; NF-kappa B; ENDOTHELIAL GROWTH-FACTOR; NF-KAPPA-B; ACUTE MYOCARDIAL-INFARCTION; NECROSIS-FACTOR-ALPHA; E3 UBIQUITIN LIGASES; MESSENGER-RNA LEVELS; HEAT-SHOCK-PROTEIN; GENE-THERAPY; MAP KINASE; SIGNAL-TRANSDUCTION;

D O I：

10.1007/s00395-020-0804-4

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 Peli1(fl/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, Peli1(fl/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 Peli1(fl/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.

引用

页数：15

共 1 条

[1] 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
Vaithinathan Selvaraju
Mahesh Thirunavukkarasu
Mandip Joshi
Babatunde Oriowo
Inam A. Shaikh
Muhammad Tipu Rishi
Leonidas Tapias
Vladimir Coca-Soliz
Ibnalwalid Saad
Jacob Campbell
Seetur R. Pradeep
Santosh Swaminathan
Siu-Pok Yee
David W. McFadden
J. Alexander Palesty
Nilanjana Maulik
Basic Research in Cardiology, 2020, 115

← 1 →