Grant: Operating Grant

Hydrogen sulfide (H2S) is conventionally known as an air pollutant. Recent studies have shown that this molecule of gas in fact is produced in our body. Cystathionine gamma-lyase (CSE) is the key enzyme for the production of H2S in cardiovascular system. The importance of H2S in regulating cardiovascular function has been extensively acknowledged as this gas molecule offers protection against hypertension, cardiac infarction, oxidative stress and inflammation. This project will test the hypothesis that reduced vascular production of H2S constitutes a predisposal factor for the occurrence of atherosclerosis, a vascular disease characterized with vascular inflammation, lipid and cholesterol deposition, and narrowing and stiffing of blood vessels. We will firstly examine the development of atherosclerosis in genetically engineered mice that do not possess the CSE gene. As such, the proposed protective effect of H2S against atherosclerosis development in these animals would have vanished. We will then investigate the mechanisms by which H2S limits atherosclerosis development. These hypothesized mechanisms include the interaction of H2S with apolipoprotein E (a polypeptide that limits the onset of hyperlipidaemia and atherosclerosis), prevention of endothelial dysfunction and smooth muscle proliferation, inhibition of the expression of adhesion molecules, and anti-oxidant and anti-inflammation protection. Finally, we will use H2S-based therapeutic approaches to prevent and treat atherosclerosis in different animal models. This project will delineate the importance of CSE/H2S pathway and its interaction with apolipoprotein E in the regulation of atherosclerosis development and the underlying molecular mechanisms. To reveal a causative relationship between vascular H2S production and atherosclerosis development may also provide a new approach for the treatment and prevention of this vascular disease.