10, 12, 15 Some chemical modulators influenced its concentration, such as physical training, erythropoietin, estrogen, granulocyte macrophage colony-stimulating factor (GM-CSF), stromal cell-derived factor −1 (SDF-1) and vascular endothelial growth factor (VEGF). Their mobilization and differentiation are triggered by many proinflammatory chemoattractants produced by traumatic and hypoxic tissue response. 17, 32 As a response to repaired damages, bone marrow released myeloid cells which contribute to re-endothelialization, known as endothelial progenitor cell (EPC). 14 While the apoptosis of endothelial cells began, it lost their attachments from basal membranes and circulated in the blood, called circulating endothelial cell (CEC). 6, 16 It starts the formation of atherosclerosis plaque. 10, 13 It lowered nitric oxide (NO) level and contributed to endothelial dysfunction, low-grade inflammation, platelet hyperactivity, tissue hypoxia, apoptosis and thrombogenesis. 12 Excessive ROS causes accelerated damages to the lipid membranes, enzymes and nucleic acids. The increase of ROS level has a harmful effect on endothelial function. 7, 9 – 11 Excess vascular production of ROS increased glucose metabolism and another form of sugar through polyol pathway, increased production of advanced glycation end products (AGEs), increased expression of the receptor for AGEs (RAGE), activated protein kinase C (PKC) isoforms and over-activated the hexosamine pathway. 30, 31 In fact, vascular walls have enzymatic systems capable of producing ROS, for example, mitochondrial electron transport chain, NADPH oxidases and xanthine oxidase. 3 The mortality in DMT2 is related to the complications, impact on vascular circumstances initiated by circulating cell at an early state. 10, 15, 46 Based on basic health research 2013, the prevalence of diabetes in Indonesia increased twice than that in 2007 (1.1–2.1%). 1, 2, 5, 29 Oxidative stress in DMT2 is caused by the accumulation of unstable residual DMT2, which is a major problem worldwide. 4 The number of patients with DM increased to 422 million in 2014 and caused 1.5 million deaths in 2015. 28 Previous research reported that patients with diabetes mellitus (DM) have a decreased life expectancy up to 7–8 years compared to those without DM. Type 2 diabetes mellitus (DMT2) is one of the major risk factors of cardiovascular diseases.
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