**4.3 Endothelial dysfunction, epigenetic modifications, and vascular calcification**

Epigenetic modifications such as DNA methylation and histone acetylation are described. Previous studies have recognized changes in expression of methyltransferase linked with hypomethylation of hypermethylated genomic regions. These findings are linked between epigenetic modifications and atherosclerosis.

Vascular calcification (VC) is one of the mechanisms that influences vascular remodeling due to the differentiation of vascular smooth muscle cells (VSMCs), alterations in elastin, collagen, and endothelial dysfunction. VC increases the chances of cardiovascular mortality and morbidity, especially in individuals with obesity, type 2 diabetes mellitus (T2DM), and chronic kidney disease [25]. Several studies have identified the correlation between ROS generation, particularly H2 O2 (hydrogen peroxide), and the progression of vascular calcification. An elevated level of ROS triggers MMP (matrix metalloproteinase) activity and alteration in collagen and elastin deposition [26].
