Interleukin 10 Attenuates Angiotensin II‐Induced Aortic Remodelling by Inhibiting Oxidative Stress‐Induced Activation of the Vascular p38 and NF‐<i>κ</i>B Pathways
Ming Qiu, Huanyu Shu, Lu Li, Yejiao Shen, Yunfan Tian, Yue Ji, Wei Sun, Yan Lu, Xiangqing Kong
Abstract
Interleukin 10 (IL‐10) is a probable anti‐inflammatory factor that can attenuate hypertrophic remodelling caused by overloaded pressure and improve cardiac function. In this study, IL‐10 was decreased in both the plasma of hypertensive patients and the aortic vessels of angiotensin II (Ang II)‐induced hypertensive mice. IL‐10 was unable to alter blood pressure in the case of Ang II‐induced hypertension. The aortic thickness, collagen deposition, and the levels of fibrosis‐associated markers, including collagen type I α 1 (Col1 α 1), connective tissue growth factor (CTGF), transforming growth factor‐ β (TGF‐ β ), and matrix metalloproteinase 2 (MMP2), were significantly reduced in the IL‐10 treatment group compared with the vehicle group after Ang II treatment. Moreover, IL‐10 treatment significantly inhibited the number of CD45 + positive cells and the mRNA expression levels of proinflammatory cytokines in the vascular tissue of Ang II‐infused mice. Furthermore, dihydroethidium (DHE) and 4hydroxynonenal (4‐HNE) staining showed that IL‐10 decreased Ang II‐induced vascular oxidative stress and lipid peroxidation. Furthermore, IL‐10 suppressed Ang II‐induced proliferation, fibrosis, and inflammation of mouse vascular adventitial fibroblasts (mVAFs). Mechanistically, IL‐10 suppressed the phosphorylation of p38 mitogen‐activated protein (MAP) kinase and nuclear factor‐ κ B (NF‐ κ B) in Ang II‐induced vascular fibrosis. In summary, our data indicated that IL‐10, as a potential therapeutic target treatment, could limit the progression of Ang II‐induced aortic remodelling.