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Inhibition of CCR8 attenuates Ang Ⅱ-induced vascular smooth muscle cell injury by suppressing the MAPK/NF-κB pathway.


ABSTRACT:

Objectives

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-α. Reactive oxygen species (ROS) kit was employed to measure ROS generation.

Results

The results revealed that CCR8 was highly expressed in diabetics and Ang Ⅱ-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-κB signaling pathway.

Conclusion

Inhibition of CCR8 attenuates Ang II-induced VSMCs injury by inhibiting the MAPK/NF-κB 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.

SUBMITTER: Liao L 

PROVIDER: S-EPMC9526881 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Inhibition of CCR8 attenuates Ang Ⅱ-induced vascular smooth muscle cell injury by suppressing the MAPK/NF-κB pathway.

Liao Lisi L   Song Di D   Shi Bobo B   Chen Ming M   Wu Linghu L   Xu Jinfeng J   Dong Fajin F  

Iranian journal of basic medical sciences 20220901 9


<h4>Objectives</h4>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.<h4>Materials and methods</h4>The expression of CCR8 was analyzed in diabetics and normal people by RT-PCR and ELISA. CCK-8 assay and transwell were  ...[more]

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