Ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction

Elham Zarrinpashneh, Tommaso Poggioli, Padmini Sarathchandra, Jonas Lexow, Laurent Monassier, Cesare Terracciano, Florian Lang, Federico Damilano, Jessica Q Zhou, Anthony Rosenzweig, Nadia Alicia Rosenthal, Maria Paola Santini

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Abstract

Serum and glucocorticoid inducible kinase 1 (SGK1) plays a pivotal role in early angiogenesis during embryonic development. In this study, we sought to define the SGK1 downstream signalling pathways in the adult heart and to elucidate their role in cardiac neo-angiogenesis and wound healing after myocardial ischemia. To this end, we employed a viable SGK1 knockout mouse model generated in a 129/SvJ background. Ablation of SGK1 in these mice caused a significant decrease in phosphorylation of SGK1 target protein NDRG1, which correlated with alterations in NF-kappaB signalling and expression of its downstream target protein, VEGF-A. Disruption of these signalling pathways was accompanied by smaller heart and body size. Moreover, the lack of SGK1 led to defective endothelial cell (ECs) migration and tube formation in vitro, and increased scarring with decreased angiogenesis in vivo after myocardial infarct. This study underscores the importance of SGK1 signalling in cardiac neo-angiogenesis and wound healing after an ischemic insult in vivo.
Original languageEnglish
Article numbere80268
Number of pages13
JournalPLoS ONE
Volume8
Issue number11
DOIs
Publication statusPublished - 2013

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