Fig. 6
Graphical summary: impact of hydrochloric- and lactic acidosis on HAoSMCs. Extracellular acidification (pH 6.8) resulted in intracellular acidification by both forms of acidosis, without counter-regulation of the cells, leading to a pHi of 6.8. Hydrochloric and lactic acidosis treatment led to an altered cell metabolism with reduced glucose and glutamine consumption. However, the effect is much more pronounced in lactic acidosis than in hydrochloric acidosis due to a reduced NAD+ /NADH ratio leading to inhibition of glycolysis. In hydrochloric acidosis, the cells manage to keep the ATP content constant, whereas this is no longer possible in lactic acidosis. This results in a substantially larger number of DEG for lactic acidosis (1633 DEG) compared to hydrochloric acidosis (492 DEG). Cells respond to metabolic-induced transcriptome changes with phenotypic changes (e.g. cellular senescence, vascular calcification) that are again more pronounced in lactic acidosis