Effects of hyperlipidemia and hyperglycaemia-induced oxidative stress on endothelial dysfunction

The endothelium consists of a single layer of endothelial cells lining the inner surface of blood vessels and lymphatic vessels. While endothelial tissue appears to be a physical barrier, it is also the place where some vasoactive compounds are created and released. Decreased nitric oxide expression and bioavailability and loss of normal endothelial-dependent vasodilatation responses of acetylcholine usually occur. While the amount of serum nitric oxide (NO) decreases, the levels of endothelin-1 (ET-1) increase and as a result of this imbalance, vasodilation deteriorates, adhesion molecules increase and endothelial functions are impaired. Oxidative stress is the most common underlying cause of endothelial dysfunction that initiates this complex process. With prolonged exposure to high glucose concentration, free fatty acid accumulation can cause changes in the availability of metabolic substrate, and these changes cause oxidative stress. In our study, we investigated the effect of high glucose and free fatty acid on the formation of endothelial diffusion in HUVECs by exposing them to 0.25, 0.5 and 1 mM PA (24 hours), which were grown in a medium containing high glucose and a medium containing relatively low glucose. For this, we determined the gene expression levels of ET-1, eNOS, VCAM, PAI-1 and proinflammatory cytokines TNF-a and IL-6, which play a key role in endothelial dysfunction, using Real Time PCR method. In conclusion, in our study, it was revealed that the increase in the expression levels of ET-1, PAI-1 and TNF ‐ a genes in HUVEC cells exposed to high concentrations of glucose and palmitic acid is more effective on endothelial dysfunction when high concentration glucose and free fatty acids are present in these cells.