Abstract 323: Hydrogen Sulfide Limits the Development of Intimal Hyperplasia in a Mouse Model of Femoral Wire Injury and in Human Veins

Abstract

Objectives: Mainstays of contemporary therapies for this arterial occlusive disease include angioplasties, stents, endarterectomies and bypass surgery. However, these treatments suffer from high failure rates due to re-occlusive vascular wall adaptations, namely intimal hyperplasia (IH). IH develops in response to endothelium injury, leading to inflammation, vascular smooth muscle cells (VSMC) dedifferentiation, migration and proliferation at the site of injury. Hydrogen sulfide (H 2 S) is a ubiquitous signaling gazotransmitter, which exhibits antioxidant, anti-inflammatory, and vaso-relaxant properties. Thus, we hypothesized that H 2 S could reduce IH formation. Methods: WT male C57BL6/J mice submitted to femoral wire injury surgery to induce IH were treated with an H 2 S donor (NaHS) in the drinking water. IH was measured 28 days post-surgery by histology. In addition, segments of great saphenous vein obtained from patients undergoing bypass surgery were maintained in culture ex-vivo for 7days in presence of various H 2 S donors (NaHS, GYY4137, diacyltrisulfide). Finally, primary human umbilical vein endothelial cells (HUVEC) and primary human VSMC were treated in-vitro with the same H 2 S donors to study cellular proliferation and migration. Results: NaHS treatment significantly reduced IH development in the mouse model of femoral wire injury ( Figure 1 ). Similarly, the various H 2 S donors prevented the development of IH in vein segments ex-vivo. In vitro , the same H 2 S donors stimulated human endothelial cells (HUVEC) migration and proliferation, while inhibiting migration and proliferation of primary VSMC ( Figure 2 ). Conclusions: Exogenous H 2 S prevents IH formation in mice in-vivo and in human veins ex-vivo . Importantly, H 2 S reduces VSMCs but stimulates ECs proliferation and migration. These data suggest that exogenous H 2 S therapy could be used in human to minimize IH, thus limiting vascular reconstruction failure.