Abl kinases are required for vascular function, Tie2 expression, and angiopoietin-1-mediated survival.

Journal Article (Journal Article)

Endothelial dysfunction is associated with diverse cardiovascular pathologies. Here, we show a previously unappreciated role for the Abelson (Abl) family kinases (Abl and Arg) in endothelial function and the regulation of angiogenic factor pathways important for vascular homeostasis. Endothelial Abl deletion in Arg-null mice led to late-stage embryonic and perinatal lethality, with mutant mice displaying focal loss of vasculature and tissue necrosis. Loss of Abl kinases led to increased endothelial cell apoptosis both in vitro and in vivo, contributing to vascular dysfunction, infarction, and tissue damage. Mechanistically, we identify a unique dual role for Abl kinases in the regulation of angiopoietin/Tie2 protein kinase signaling. Endothelial Abl kinases modulate Tie2 expression and angiopoietin-1-mediated endothelial cell survival. These findings reveal a critical requirement for the Abl kinases in vascular development and function, which may have important implications for the clinical use of Abl kinase inhibitors.

Full Text

Duke Authors

Cited Authors

  • Chislock, EM; Ring, C; Pendergast, AM

Published Date

  • July 23, 2013

Published In

Volume / Issue

  • 110 / 30

Start / End Page

  • 12432 - 12437

PubMed ID

  • 23840065

Pubmed Central ID

  • PMC3725093

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1304188110


  • eng

Conference Location

  • United States