Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cystathionine gamma lyase is regulated by flow and controls smooth muscle migration in human saphenous vein

Shuang Zhao
ORCID logo ,
Céline Deslarzes-Dubuis
,
Severine Urfer
,
Martine Lambelet
ORCID logo ,
Sébastien Déglise
,
Florent Allagnat
* ORCID logo
Version 1 : Received: 12 July 2023 / Approved: 14 July 2023 / Online: 14 July 2023 (07:58:32 CEST)

A peer-reviewed article of this Preprint also exists.

Zhao, S.; Deslarzes-Dubuis, C.; Urfer, S.; Lambelet, M.; Déglise, S.; Allagnat, F. Cystathionine Gamma Lyase Is Regulated by Flow and Controls Smooth Muscle Migration in Human Saphenous Vein. Antioxidants 2023, 12, 1731. Zhao, S.; Deslarzes-Dubuis, C.; Urfer, S.; Lambelet, M.; Déglise, S.; Allagnat, F. Cystathionine Gamma Lyase Is Regulated by Flow and Controls Smooth Muscle Migration in Human Saphenous Vein. Antioxidants 2023, 12, 1731.

Abstract

The saphenous vein is the conduit of choice for bypass grafting. Unfortunately, the hemodynamic stress associated with the arterial environment of the bypass vein graft leads to the development of intimal hyperplasia (IH), an excessive cellular growth and collagen deposition that results in restenosis and secondary graft occlusion. Hydrogen sulfide (H2S) is a ubiquitous redox-modifying gasotransmitter that inhibits IH. H2S is produced via the reverse trans-sulfuration pathway by 3 enzymes: cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST). However, the expression and regulation of these enzymes in the human vasculature remains unclear. Here, we investigated the expression of CSE, CBS and 3-MST in segments of native human saphenous vein and large arteries. Furthermore, we evaluated the regulation of these enzymes in vein segments cultured under static, venous (7 mmHg pressure) or arterial (100 mmHg pressure) pressure. CSE was expressed in the media, neointima and intima of the vessels and was negatively regulated by arterial shear stress. Adenoviral-mediated CSE overexpression or RNA interference-mediated CSE knock-down revealed that CSE inhibited primary human VSMC migration but not proliferation. We propose that high shear stress in arteriovenous bypass grafts inhibits CSE expression in both the media and endothelium, which may contribute to increased VSMC migration in the context of IH.

Keywords

Hydrogen sulfide (H2S), Cystathionine gamma-Lyase, intimal hyperplasia, venous bypass

Subject

Biology and Life Sciences, Anatomy and Physiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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