Hydrogen sulfide-releasing peptide hydrogel limits the development of intimal hyperplasia in human vein segments.

Details

Serval ID
serval:BIB_EE4541E87F23
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Hydrogen sulfide-releasing peptide hydrogel limits the development of intimal hyperplasia in human vein segments.
Journal
Acta biomaterialia
Author(s)
Longchamp A., Kaur K., Macabrey D., Dubuis C., Corpataux J.M., Déglise S., Matson J.B., Allagnat F.
ISSN
1878-7568 (Electronic)
ISSN-L
1742-7061
Publication state
Published
Issued date
01/10/2019
Peer-reviewed
Oui
Volume
97
Pages
374-384
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Abstract
Currently available interventions for vascular occlusive diseases suffer from high failure rates due to re-occlusive vascular wall adaptations, a process called intimal hyperplasia (IH). Naturally occurring hydrogen sulfide (H <sub>2</sub> S) works as a vasculoprotective gasotransmitter in vivo. However, given its reactive and hazardous nature, H <sub>2</sub> S is difficult to administer systemically. Here, we developed a hydrogel capable of localized slow release of precise amounts of H <sub>2</sub> S and tested its benefits on IH. The H <sub>2</sub> S-releasing hydrogel was prepared from a short peptide attached to an S-aroylthiooxime H <sub>2</sub> S donor. Upon dissolution in aqueous buffer, the peptide self-assembled into nanofibers, which formed a gel in the presence of calcium. This new hydrogel delivered H <sub>2</sub> S over the course of several hours, in contrast with fast-releasing NaHS. The H <sub>2</sub> S-releasing peptide/gel inhibited proliferation and migration of primary human vascular smooth muscle cells (VSMCs), while promoting proliferation and migration of human umbilical endothelial cells (ECs). Both NaHS and the H <sub>2</sub> S-releasing gel limited IH in human great saphenous vein segments obtained from vascular patients undergoing bypass surgery, with the H <sub>2</sub> S-releasing gel showing efficacy at a 5x lower dose than NaHS. These results suggest local perivascular H <sub>2</sub> S release as a new strategy to limit VSMC proliferation and IH while promoting EC proliferation, hence re-endothelialization. STATEMENT OF SIGNIFICANCE: Arterial occlusive disease is the leading cause of death in Western countries, yet current therapies suffer from high failure rates due to intimal hyperplasia (IH), a thickening of the vascular wall leading to secondary vessel occlusion. Hydrogen sulfide (H <sub>2</sub> S) is a gasotransmitter with vasculoprotective properties. Here we designed and synthesized a peptide-based H <sub>2</sub> S-releasing hydrogel and found that local application of the gel reduced IH in human vein segments obtained from patients undergoing bypass surgery. This work provides the first evidence of H <sub>2</sub> S efficacy against IH in human tissue, and the results show that the gel is more effective than NaHS, a common instantaneous H <sub>2</sub> S donor.
Keywords
Human Umbilical Vein Endothelial Cells/metabolism, Human Umbilical Vein Endothelial Cells/pathology, Humans, Hydrogels/chemistry, Hydrogels/pharmacokinetics, Hydrogels/pharmacology, Hydrogen Sulfide/chemistry, Hydrogen Sulfide/pharmacokinetics, Hydrogen Sulfide/pharmacology, Hyperplasia, Peptides/chemistry, Peptides/pharmacokinetics, Peptides/pharmacology, Tunica Intima/metabolism, Tunica Intima/pathology, Veins/metabolism, Veins/pathology, Hydrogel, Hydrogen sulfide, Intimal hyperplasia, Proliferation, Smooth muscle cells
Pubmed
Web of science
Create date
07/03/2021 13:25
Last modification date
08/03/2021 7:26
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