[HTML][HTML] Angiopoietin-1 is essential in mouse vasculature during development and in response to injury

M Jeansson, A Gawlik, G Anderson… - The Journal of …, 2011 - Am Soc Clin Investig
M Jeansson, A Gawlik, G Anderson, C Li, D Kerjaschki, M Henkelman, SE Quaggin
The Journal of clinical investigation, 2011Am Soc Clin Investig
Angiopoietin-1/Tek signaling is a critical regulator of blood vessel development, with
conventional knockout of angiopoietin-1 or Tek in mice being embryonically lethal due to
vascular defects. In addition, angiopoietin-1 is thought to be required for the stability of
mature vessels. Using a Cre-Lox conditional gene targeting approach, we have studied the
role of angiopoietin-1 in embryonic and adult vasculature. We report here that angiopoietin-
1 is critical for regulating both the number and diameter of developing vessels but is not …
Angiopoietin-1/Tek signaling is a critical regulator of blood vessel development, with conventional knockout of angiopoietin-1 or Tek in mice being embryonically lethal due to vascular defects. In addition, angiopoietin-1 is thought to be required for the stability of mature vessels. Using a Cre-Lox conditional gene targeting approach, we have studied the role of angiopoietin-1 in embryonic and adult vasculature. We report here that angiopoietin-1 is critical for regulating both the number and diameter of developing vessels but is not required for pericyte recruitment. Cardiac-specific knockout of angiopoietin-1 reproduced the phenotype of the conventional knockout, demonstrating that the early vascular abnormalities arise from flow-dependent defects. Strikingly, deletion in the entire embryo after day E13.5 produced no immediate vascular phenotype. However, when combined with injury or microvascular stress, angiopoietin-1 deficiency resulted in profound organ damage, accelerated angiogenesis, and fibrosis. These findings redefine our understanding of the biological roles of angiopoietin-1: it is dispensable in quiescent vessels but has a powerful ability to modulate the vascular response after injury.
The Journal of Clinical Investigation