Environmental dose of 16 priority-controlled PAHs induce endothelial dysfunction: An in vivo and in vitro study

Polycyclic aromatic hydrocarbons (PAHs) exposure is related to the occurrence of cardiovascular diseases (CVDs). Endothelial dysfunction is considered an initial event of CVDs. To confirm the relationship of PAHs exposure with endothelial dysfunction, 8-week-old male SD rats and primary human umbilical vein endothelial cells (HUVECs) were co-treated with environmental doses of 16 priority-controlled PAHs for 90 d and 48 h, respectively. Results showed that 10× PAHs exposure remarkably raised tumor necrosis factor-α and malonaldehyde levels in rat serum (p < 0.05), but had no effects on interleukin-8 levels and superoxide dismutase activity. The expressions of SIRT1 in HUVECs and rat aorta were attenuated after PAHs treatment. Interestingly, PAHs exposure did not activate the expression of total endothelial nitric oxide synthase (eNOS), but 10× PAHs exposure significantly elevated the expression of phosphorylated eNOS (Ser1177) in HUVECs and repressed it in aortas, accompanied with raised nitrite level both in serum and HUVECs by 48.50–253.70 %. PAHs exposure also led to the augment of endothelin-1 (ET-1) levels by 19.76–38.54 %, angiotensin (Ang II) levels by 20.09–39.69 % in HUVECs, but had no effects on ET-1 and Ang II levels in serum. Additionally, PAHs exposure improved endocan levels both in HUVECs and serum by 305.05–620.48 % and stimulated the THP-1 cells adhered to HUVECs (p < 0.05). After PAHs treatment, the smooth muscle alignment was disordered and the vascular smooth muscle locally proliferated in rat aorta. Notably, the systolic blood pressure of rats exposed to 10× PAHs increased significantly compared with the control ones (131.28 ± 5.20 vs 116.75 ± 5.33 mmHg). In summary, environmental chronic PAHs exposure may result in endothelial dysfunction in SD rats and primary HUVECs. Our research can confirm the cardiovascular damage caused by chronic exposure to PAHs and provide ideas for the prevention or intervention of CVDs affected by environmental factors.