PL03 Expression of H2S-catalyzing enzymes during “acute chronic disease”

Abstract

Disturbed endogenous H2S production as a result down-regulation of the H2S-catalyzing enzymes cysthathionine-γ-lyase (CSE) and cysthathione-β-synthase (CBS) is associated with chronic cardiovascular pathology, e.g. hypertension, atherosclerosis, and chronic kidney disease [1] , [2] , [3] . CSE and CBS up-regulation was found during acute hyperinflammatory states resulting from circulatory shock [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , but little is known on the effect of acute stress states on CSE and CBS expression during chronic disease. Therefore we measured CBS and CSE expression before and after porcine kidney ischemia/reperfusion (I/R) injury comparing otherwise healthy animals and swine with ubiquitous atherosclerosis resulting from a mutation of the LDL receptor together with a cholesterol-enriched diet [12] , [13] . CBS expression was not present in native biopsies, and minimal only post I/R, i.e. in necrotic tubules and cells only. Atherosclerotic swine had lower CSE expression in native biopsies. I/R injury caused a down-regulation of the CSE enzyme in both groups, which was more pronounced in the atherosclerotic animals. In the atherosclerotic swine fecal peritonitis-induced septic shock also caused marked down-regulation of kidney CSE expression when compared to sham-operated animals. Therefore, the effect of H2S-supplementation using the slow-releasing H2S donor GYY4137 [14] in atherosclerotic swine with septic shock will be shown. GYY4137 is used to avoid the short and high and therefore potentially deleterious peak sulfide concentrations associated with NaSH or Na2S administration. Equivocal data are available on H2S-catalyzing enzymes during cigarette smoke-induced lung disease: both reduced [15] , [16] and increased [16] , [17] CSE expression were reported. So far, no data are available whether chronic lung disease affects the otherwise pronounced increase in CSE and CBS expression after trauma [18] or sepsis [4] , [5] , [6] , [7] , [10] , [11] . Therefore, the effects of genetic CSE deletion and H2S-supplementation using the slow-releasing H2S donor GYY4137 in mice with cigarette smoke-induced COPD undergoing pressure wave-generated blunt chest trauma [18] will be shown.