Ablation of SGK1 Impairs Endothelial Cell Migration and Tube Formation Leading to Decreased Neo-Angiogenesis Following Myocardial Infarction

• Published in: PloS one Vol. 8; no. 11; p. e80268
• Main Authors: Zarrinpashneh, Elham, Poggioli, Tommaso, Sarathchandra, Padmini, Lexow, Jonas, Monassier, Laurent, Terracciano, Cesare, Lang, Florian, Damilano, Federico, Zhou, Jessica Q., Rosenzweig, Anthony, Rosenthal, Nadia, Santini, Maria Paola
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.11.2013; Public Library of Science (PLoS)
• Subjects: Ablation; Analysis; Angiogenesis; Animals; Body size; Cancer; Cardiology; Cardiology and cardiovascular system; Cell adhesion & migration; Cell Cycle Proteins - metabolism; Cell migration; Cell Movement - genetics; Cell Size; Disease Models, Animal; Downstream; Embryogenesis; Embryonic growth stage; Endothelial cells; Endothelial Cells - metabolism; Endothelium; Fibrosis; Gene expression; Glucocorticoids; Heart; Heart attack; Heart diseases; Human health and pathology; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; In vivo methods and tests; Intracellular Signaling Peptides and Proteins - metabolism; Ischemia; Kinases; Life Sciences; Mice; Mice, Knockout; Myocardial infarction; Myocardial Infarction - genetics; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial ischemia; Myocardial Ischemia - genetics; Myocardial Ischemia - metabolism; Myocardial Ischemia - pathology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; NF-kappa B - metabolism; NF-κB protein; Phenotype; Phosphorylation; Physiology; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proteins; Proteomics; Rodents; Scars; Science; Signal Transduction; Signaling; Vascular endothelial growth factor; Wound healing; United Kingdom > UK; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0080268

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-κB 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.