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

Autor:	Atchison L; Department of Biomedical Engineering, Duke University, Durham, NC, USA., Abutaleb NO; Department of Biomedical Engineering, Duke University, Durham, NC, USA., Snyder-Mounts E; Department of Biomedical Engineering, Duke University, Durham, NC, USA., Gete Y; Department of Cell Biology and Molecular Genetics at University of Maryland, College Park, MD, USA., Ladha A; Department of Biomedical Engineering, Duke University, Durham, NC, USA., Ribar T; Duke iPSC Shared Resource Facility at Duke University, Durham, NC, USA., Cao K; Department of Cell Biology and Molecular Genetics at University of Maryland, College Park, MD, USA., Truskey GA; Department of Biomedical Engineering, Duke University, Durham, NC, USA. Electronic address: george.truskey@duke.edu.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2020 Feb 11; Vol. 14 (2), pp. 325-337. Date of Electronic Publication: 2020 Feb 06.
DOI:	10.1016/j.stemcr.2020.01.005
Abstrakt:	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. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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