Hydrogen sulfide attenuates ferric chloride-induced arterial thrombosis in rats

ABSTRACT

Hydrogen sulfide (H₂S) is a novel gaseous transmitter, regulating a multitude of biological processes in the cardiovascular and other systems. However, it remains unclear whether it exerts any effect on arterial thrombosis. In this study, we examined the effect of H₂S on ferric chloride (FeCl₃)-induced thrombosis in the rat common carotid artery (CCA). The results revealed a decrease of the H₂S-producing enzyme cystathionine γ-lyase (CSE) expression and H₂S production that persisted until 48 h after FeCl₃ application. Intriguingly, administration with NaHS at appropriate regimen reduced the thrombus formation and enhanced the blood flow, accompanied with the alleviation of CSE and CD31 downregulation, and endothelial cell apoptosis in the rat CCA following FeCl₃ application. Moreover, the antithrombotic effect of H₂S was also observed in Rose Bengal photochemical model in which the development of thrombosis is contributed by oxidative injury to the endothelium. The in vitro study demonstrated that the mRNA and protein expression of CSE, as well as H₂S production, was decreased in hydrogen peroxide (H₂O₂)-treated endothelial cells. Exogenous supplement of NaHS and CSE overexpression consistently alleviated the increase of cleaved caspase-3 and endothelial cell damage caused by H₂O₂. Taken together, our findings suggest that endogenous H₂S generation in the endothelium may be impaired during arterial thrombosis and that modulation of H₂S, either exogenous supplement or boost of endogenous production, may become a potential venue for arterial thrombosis therapy.

KEYWORDS:

• Arterial thrombosis
• CSE
• endothelial cell
• hydrogen sulfide
• oxidative stress

Disclosure statement

No potential conflict of interest exists.

Funding information

The work was funded by Suzhou Medical Key discipline Project, Science and Education Methodist Youth Science and Technology Project of Suzhou Health Bureau (KJXW2011010). It was also supported in part by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

ORCID

Li-Fang Hu http://orcid.org/0000-0001-8326-7779