Therapeutic potential of hydrogen sulfide in peripheral vascular diseases
Arterial occlusive disease is the leading cause of death in Western countries. Mainstays of contemporary therapies for this 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 vessel injury, leading to inflammation, vascular smooth muscle cells dedifferentiation, migration and proliferation into the vessel's innermost layer or intima.
Re-occlusive IH lesions result in costly and complex recurrent end-organ ischemia, and often lead to loss of limb, brain function, or life. Despite decades of IH research, limited therapies are currently available.
The laboratory of vascular surgery (CHUV, Lausanne, http://cvalab.strikingly.com) aims at developing new strategies to treat re-occlusive IH lesions.
Hydrogen Sulfide (H2S) is a gas easily identified by its distinctive odor of rotten eggs. H2S naturally occurs in mammalian tissue as a byproduct of cysteine metabolism via the enzymes cystathionine-β-synthase (CBS) and cystathionine gamma-lyase (CGL). This endogenous H2S production is now recognized as having multiple cytoprotective properties.
This project is designed to assess the therapeutic relevance of exogenous H2S in the prevention of IH. We further aim to design therapies to stimulate endogenous H2S production and protect from IH.
We specialize in mouse models of microsurgery and in vitro studies on human veins and primary vascular cells.
Benefits of Hydrogen Sulfide in Kidney Transplantation
Recently we and others demonstrated that Hydrogen Sulfide (H2S) protects from IRI in rodent models. We propose to test the benefits of H2S against IRI using our preclinical models of pig and mouse kidney transplant model. These data can serve as a basis for future H2S-based therapies for transplantation, and carry high significance in reducing the burden of kidney failure and improving outcomes in renal transplant patients.