Fig. 7: Schematic diagram summarising atherogenesis in the vasculature of MELAS patients. LDL gets oxidised to form ox-LDL by high levels of ROS in the environment.

High levels of ox-LDL will be produced overtime and will accumulate in the ECs and subsequently, enters the sub-endothelial space. In tandem, monocytes in circulation attaches to activated ECs and become macrophages. High expression of ‘pro-adhesive’ VCAM-1 in these activated ECs promotes more monocytes to adhere to the endothelium. Large numbers of monocytes and macrophages creates a pro-inflammatory niche characterised by higher expression of chemokine IL-8. These macrophages then transmigrate into the sub-endothelial space where they are loaded with pathological levels of ox-LDL. Because of high lipid load, these macrophages transform into foam cells. Accumulation of foam cells in the vasculature overtime causes formation of the fatty streak and subsequently, an atherosclerosis plaque