iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome.

Journal Article (Journal Article)

Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder caused by a point mutation in the Lamin A gene that produces the protein progerin. Progerin toxicity leads to accelerated aging and death from cardiovascular disease. To elucidate the effects of progerin on endothelial cells, we prepared tissue-engineered blood vessels (viTEBVs) using induced pluripotent stem cell-derived smooth muscle cells (viSMCs) and endothelial cells (viECs) from HGPS patients. HGPS viECs aligned with flow but exhibited reduced flow-responsive gene expression and altered NOS3 levels. Relative to viTEBVs with healthy cells, HGPS viTEBVs showed reduced function and exhibited markers of cardiovascular disease associated with endothelium. HGPS viTEBVs exhibited a reduction in both vasoconstriction and vasodilation. Preparing viTEBVs with HGPS viECs and healthy viSMCs only reduced vasodilation. Furthermore, HGPS viECs produced VCAM1 and E-selectin protein in TEBVs with healthy or HGPS viSMCs. In summary, the viTEBV model has identified a role of the endothelium in HGPS.

Full Text

Duke Authors

Cited Authors

  • Atchison, L; Abutaleb, NO; Snyder-Mounts, E; Gete, Y; Ladha, A; Ribar, T; Cao, K; Truskey, GA

Published Date

  • February 2020

Published In

Volume / Issue

  • 14 / 2

Start / End Page

  • 325 - 337

PubMed ID

  • 32032552

Pubmed Central ID

  • PMC7013250

Electronic International Standard Serial Number (EISSN)

  • 2213-6711

International Standard Serial Number (ISSN)

  • 2213-6711

Digital Object Identifier (DOI)

  • 10.1016/j.stemcr.2020.01.005


  • eng