2. Academic Validation
  3. Restoration of ARA metabolic disorders in vascular smooth muscle cells alleviates intimal hyperplasia

Restoration of ARA metabolic disorders in vascular smooth muscle cells alleviates intimal hyperplasia

  • Eur J Pharmacol. 2024 Nov 15:983:176824. doi: 10.1016/j.ejphar.2024.176824.
Hui Wu 1,  Dai Li 2,  Chen-Yu Zhang 3,  Ling-Li Huang 1,  You-Jie Zeng 4,  Tian-Ge Chen 5,  Ke Yu 1,  Jia-Wei Meng 1,  Yu-Xin Lin 1,  Ren Guo 6,  Yong Zhou 7,  Ge Gao 8
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
  • 2 Phase I Clinical Research Center, Xiangya Hospital, Central South University, Changsha, 410005, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410005, China.
  • 3 Department of Physiology, School of Basic Medical Science, Central South University, Changsha, 410078, China.
  • 4 Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
  • 5 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410005, China.
  • 6 Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, China. Electronic address: pharmguor@csu.edu.cn.
  • 7 Department of Physiology, School of Basic Medical Science, Central South University, Changsha, 410078, China. Electronic address: zhouyong421@csu.edu.cn.
  • 8 Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410013, China. Electronic address: gaoge96@csu.edu.cn.
PMID: 39265882 DOI: 10.1016/j.ejphar.2024.176824
Abstract

Intimal hyperplasia (IH) is an innegligible issue for patients undergoing interventional therapy. The proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor-BB (PDGF-BB) are critical events in the development of IH. While the exact mechanism and effective target for IH needs further investigation. Metabolic disorders of arachidonic acid (ARA) are involved in the occurrence and progression of various diseases. In this study, we found that the expressions of soluble Epoxide Hydrolase (sEH) and cyclooxygenase-2 (COX-2) were significantly increased in the VSMCs during balloon injury-induced IH. Then, we employed a COX-2/sEH dual inhibitor PTUPB to increase the concentration of epoxyeicosatrienoic acids (EETs) while prevent the release of pro-inflammatory prostaglandins. Results showed that PTUPB treatment significantly reduced neointimal thickening induced by balloon injury in rats in vivo and inhibited PDGF-BB-induced proliferation and migration of VSMCs in vitro. Our results showed that PTUPB may reverse the phenotypic transition of VSMCs by inhibiting Pttg1 expression. In conclusion, we found that the dysfunction of ARA metabolism in VSMCs contributes to IH, and the COX-2/sEH dual inhibitor PTUPB attenuates IH progression by reversing the phenotypic switch in VSMC through the SIRT1/Pttg1 pathway.

Keywords

ARA; Intimal hyperplasia; PTUPB; Pttg1; Sirt1; VSMCs; Vascular remodeling.

Figures
Products
Inhibitors & Agonists
Other Products