Connexins as Potential Biomarkers and Therapeutic Targets for Vascular Malformation
Abstract
Blood vessels form during development through coordinated signaling between vascular endothelial cells (EC) and their adjacent cell neighbors. Inherited mutations that disrupt these signaling processes can lead to vascular malformations with profound consequences on vascular organization and function. In the rare congenital disease Hereditary Hemorrhagic Telangiectasia (HHT), loss-of-function mutations affecting the Alk1 cell surface receptor drives the appearance of disorganized vascular lesions prone to sudden, serious rupture. The goal of this study is to understand how Alk1 mutation may promote vascular malformation by dysregulating connexins (Cx), constituent proteins of vascular gap junctions that support direct cell-cell signaling of small electrochemical signals. In the second year of this study, we have made significant progress towards understanding this question. We have improved our understanding of connexins are regulated by Alk1 and VEGF signaling, and how changes in Cx expression influence EC gene expression and function. Lastly, we have developed several tools and performed proof-of-concept experiments to manipulate Cxs in 2D and organ-on-a-chip platforms.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2023
- Accession Number
- AD1203901
Entities
People
- Jennifer Fang
Organizations
- University of California, Irvine