Inhibition of CCR8 Attenuates Ang Ⅱ-induced Vascular Smooth Muscle Cell Injury by Suppressing the MAPK/NF-κB Pathway.

Objective(s): Hyperinsulinemia, secondary to insulin resistance, may lead to vascular smooth muscle cell dysfunction. In the present research, we aimed to investigate the effect of Chemokine receptor 8 (CCR8) on angiotensin II (Ang II)-induced dysfunction of vascular smooth muscle cells (VSMCs) and to explore the underlying molecular mechanism. Materials and Methods: The expression of CCR8 was analyzed in diabetics and normal people by RT-PCR and ELISA. CCK-8 assay and transwell were used to explore cell proliferation and migration, and ELISA was used to measure the content of IL-6 and TNF-alpha. Reactive oxygen species (ROS) kit was employed to measure ROS generation. Results: The results revealed that CCR8 was highly expressed in diabetics and Ang.-induced VSMCs. Further studies found that interfering with the expression of CCR8 significantly reduced the production of ROS and the levels of inflammatory factors in AngII-induced VSMCs. Interfering with CCR8 increased the glucose uptake induced by AngII+IR. More importantly, inhibition of CCR8 alleviated Ang II-induced dysfunction of VSMCs. Inhibition of CCR8 inactivated the MAPK/NF-kappa B signaling pathway. Conclusion: Inhibition of CCR8 attenuates Ang II-induced VSMCs injury by inhibiting the MAPK/NF-kappa B pathway. CCR8 may be a new biomarker related to hypertension and insulin resistance and is a new target for the treatment of human cardiovascular diseases.