Hydrogen sulfide in diabetes and cardiovascular disease

In this thesis, the role of hydrogen sulfide (H2S) is studied in the context of cardiovascular disease and diabetes-associated disease. H2S is best known for its pungent smell of rotten eggs and toxicity. However, recently it has been found that H2S is endogenously produced in the human body, and has – be it at low concentrations - a lot of beneficial properties. In this thesis, we showed that gaseous H2S is protective in an experimental animal model of myocardial infarction. Also, the urinary excretion of H2S-metabolite sulfate was measured in different patients cohorts, which showed that lower urinary sulfate is associated with diabetes, increased blood pressure, greater risk of all-cause mortality, and the onset of cardiovascular disease. However, there is also a potential disadvantage of H2S in the context of cardiovascular diseases. Within advanced atherosclerotic plaques, small blood vessels can be formed. These microvessels are a risk factor for plaque vulnerability, since they are fragile and can cause an intraplaque hemorrhage, with subsequent plaque rupture and risk of myocardial infarction or stroke. H2S promotes the formation of new blood vessels (angiogenesis), and is produced locally in the atherosclerotic plaque. We need to be aware of this potentially dangerous side effect when considering H2S-related therapies in the course of cardiovascular disease.