(525.2) Hydrostatic Pressure Controls Angiogenesis through Endothelial YAP1 during Lung Regeneration

Poster Board Number: D2
Introduction:

Tadanori Mammoto (Medical College of Wisconsin), Tendai Hunyenyiwa (Medical College of Wisconsin), Priscilla Kyi (Medical College of Wisconsin), Kathryn Hendee (Medical College of Wisconsin), Kienna Matus (Medical College of Wisconsin), Akiko Mammoto (Medical College of Wisconsin)

Pulmonary artery (PA) pressure increases during lung growth after unilateral pneumonectomy (PNX). The objective of this study is to understand the mechanism by which increases in PA pressure control angiogenesis during lung regeneration. Mechanosensitive transcriptional co-activator, yes-associated protein (YAP1), in endothelial cells (ECs) is necessary for angiogenesis during post-PNX lung growth. We investigate whether increases in PA pressure following PNX controls angiogenesis through YAP1. When hydrostatic pressure is applied to human pulmonary arterial ECs (HPAECs), the expression of YAP1, transcription factor TEAD1, and angiogenic factor receptor Tie2 increases, while these effects are inhibited when HPAECs are treated with YAP1 siRNA or YAP1S94A mutant that fails to bind to TEAD1. Hydrostatic pressure also stimulates DNA synthesis and cell migration in HPAECs, while YAP1 knockdown or YAP1S94A mutant inhibits the effects. Gene enrichment analysis reveals that the levels of extracellular matrix or cell adhesion molecules are altered in post-PNX mouse lung ECs, which interact with YAP1. These results suggest that increases in PA pressure stimulate angiogenesis through YAP1 during regenerative lung growth.

NIH R21AG054830, R01HL139638, R21AG062893, R01HL142578, AHA 18TPA34170129