Epicatechin (EPI) Induces Mitochondrial Biogenesis (MB) in Human Coronary Artery Endothelial Cells (HCAEC) Cultured Under High Glucose Conditions

Type 2 Diabetes Mellitus (DM) is the fastest growing disease in the USA. Studies demonstrate that DM patients have high cardiovascular risk and develop endothelial dysfunction (ED). Endothelial mitochondria play crucial roles in vascular function, regulating cell metabolism, redox state and signal transduction. In DM and metabolic syndrome patients, the number of mitochondria in endothelial cells is decreased favoring ED. An important link between vascular endothelium and DM is the essential role of endothelial (e)NOS‐derived nitric oxide (NO), since NO induces the activation of MB‐related signaling pathways. The flavanol EPI is capable to induce endothelial NO production. The aim of this work was to analyze EPI effects, on the mechanisms responsible for the induction of MB in a DM milleu model (High Glucose [HG]) in HCAEC. We evaluate the dependence of MB on downstream NO related pathways including p38‐MAPK, PGC1α, AMPK, Tfam and SIRT1. Our results show that in control conditions (normal glucose [NG]) EPI increases by ~30% eNOS protein levels 48 h after treatment. It also stimulates NO production, and induces increases in MB as determined by Mitotracker staining density at 48 h. Western blots of HCAEC treated with EPI for 48 h were probed with antibodies against electron transport chain proteins. The treatment appears to induce an increase on all the components of the electron transport chain. We also analyze the effects of high glucose [25 mM] (HG) on the expression of eNOS and MB related, SIRT1 and AMPK, the results show that HG decrease their expression and EPI is capable of restore these proteins expression to almost normal levels. Which suggest recovery of the endothelial function.