Inhibition of CCR۸ 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 ۸ (CCR۸) 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 CCR۸ was analyzed in diabetics and normal people by RT-PCR and ELISA. CCK-۸ assay and transwell were used to explore cell proliferation and migration, and ELISA was used to measure the content of IL-۶ and TNF-α. Reactive oxygen species (ROS) kit was employed to measure ROS generation. Results: The results revealed that CCR۸ was highly expressed in diabetics and Ang Ⅱ-induced VSMCs. Further studies found that interfering with the expression of CCR۸ significantly reduced the production of ROS and the levels of inflammatory factors in AngⅡ-induced VSMCs. Interfering with CCR۸ increased the glucose uptake induced by AngⅡ+IR. More importantly, inhibition of CCR۸ alleviated Ang II-induced dysfunction of VSMCs. Inhibition of CCR۸ inactivated the MAPK/NF-κB signaling pathway.Conclusion: Inhibition of CCR۸ attenuates Ang II-induced VSMCs injury by inhibiting the MAPK/NF-κB pathway. CCR۸ may be a new biomarker related to hypertension and insulin resistance and is a new target for the treatment of human cardiovascular diseases.

Keywords:

CCR۸ , Hypertension , Inflammation , insulin resistance , MAPK/NF-κB signaling , Oxidative