P2X7 Receptor Deficiency Mitigates High-Fat Diet-Induced Vascular Remodeling Through Inflammation and Oxidative Stress Modulation and Mathematical Model
نویسندگان
1 Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. CHINA
2 Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. CHINA
3 Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. CHINA
4 Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. CHINA
5 Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. CHINA
6 Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. CHINA
7 Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. CHINA
8 Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. CHINA
doi
10.30492/ijcce.2025.2069356.7266چکیده
High Fat Diet (HFD)-induced chronic inflammation and oxidative stress induce severe vascular remodeling. P2X7R (purinergic receptor P2X, ligand-gated ion channel, 7), an ion channel, is a key regulator of mitochondrial energy metabolism, revealing its importance for cardiovascular diseases; however, its underlying mechanism remains unclear. The study aimed to investigate the mechanism of P2X7R in HFD-induced vascular remodeling. HFD was administered for 24 weeks to induce arterial vascular remodeling in mice. Vascular Smooth Muscle Cells (VSMCs) were treated with PA to trigger inflammation, oxidative stress, and injury, helping us better understand the effects of these conditions on the cells. P2X7R deficiency significantly decreased levels of inflammation-associated cytokines and Reactive Oxygen Species (ROS) in the mice arterial tissue and vascular remodeling in HFD-treated animals. P2X7R targeted NF-κB activation and SIRT1 inhibition to facilitate PA-induced vascular impairment, according to in vitro experiments using VSMCs. HFD-induced activation of vascular remodeling was regulated by NF-κB and SIRT1, which serve a role in inflammation and oxidative stress. Mechanistically, P2X7R deficiency exerted its protective effects by inhibiting the activation of the NF-κB pathway and preventing the downregulation of SIRT1, thereby mitigating inflammation and oxidative stress, respectively. Inflammation and oxidative stress contributed to vascular remodeling in HFD-treated mice, which was prevented by P2X7R deficiency by inhibiting NF-κB activation and reversing SIRT1 inhibition.
