Regulation of blood-lymphatic endothelial identity by blood flow and hemodynamic forces / Chiu-Yu Chen.

Format:

Book

Manuscript

Thesis/Dissertation

Author/Creator:

Chen, Chiu-Yu.

Contributor:

Kahn, Mark L., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Bioengineering.

Bioengineering--Penn dissertations.

Local Subjects:

Penn dissertations--Bioengineering.

Bioengineering--Penn dissertations.

Physical Description:

vi, 100 pages : color illustrations ; 29 cm

Production:

2011.

Summary:

Blood vessels and lymphatic vessels are functionally and molecularly distinct. Blood vessels carry rapidly flowing blood and are subject to hemodynamic forces, while lymphatic vessels carry slowly moving lymph and are not exposed to significant fluid forces. During development lymphatic vessels arise from venous precursors that express PROX1, an endothelial transcription factor that is both necessary and sufficient to confer lymphatic identity ex vivo. Whether the genetic program of blood and lymphatic vessel identity is linked to their hemodynamic environment is unknown. Here we show that the mesenteric lymphatic vessels exposed to rapid blood flow in SLP-76-deficient mice lose expression of the lymphatic identity markers PROX1, LYVE1, and Podoplanin in vivo and that primary lymphatic endothelial cells exposed to similar levels of shear stress ex vivo rapidly down-regulate PROX1 expression. These findings demonstrate that blood flow can reprogram lymphatic vessels to blood vessels and suggest that hemodynamic forces may regulate the expression of vessel identity transcriptional pathways later in life.

Notes:

Adviser: Mark L. Kahn.

Thesis (Ph.D. in Bioengineering) -- University of Pennsylvania, 2011.

Includes bibliographical references.