Nanocurcumin Reduces High Glucose and Particulate Matter-Induced Endothelial Inflammation: Mitochondrial Function and Involvement of miR-221/222

Int J Nanomedicine. 2023 Dec 6:18:7379-7402. doi: 10.2147/IJN.S433658. eCollection 2023.

Abstract

Purpose: Particulate matter (PM) 2.5, harmful air pollutants, and diabetes are associated with high morbidity and mortality from cardiovascular disease (CVD). However, the molecular mechanisms underlying the combined effects of PM and diabetes on CVD remain unclear.

Methods: Endothelial cells (ECs) treated with high glucose (HG) and PM mimic hyperglycemia and air pollutant exposure in CVD. Endothelial inflammation was evaluated by Western blot and immunofluorescence of ICAM-1 expression and monocyte adhesion. The mechanisms underlying endothelial inflammation were elucidated through MitoSOX Red analysis, JC-1 staining, MitoTracker analysis, and Western blot analysis of mitochondrial fission-related, autophagy-related, and mitophagy-related proteins. Furthermore. nanocurcumin (NCur) pretreatment was used to test if it has a protective effect.

Results: ECs under co-exposure to HG and PM increased ICAM-1 expression and monocyte adhesion, whereas NCur pretreatment attenuated these changes and improved endothelial inflammation. PM exposure increased mitochondrial ROS levels, worsened mitochondrial membrane potential, promoted mitochondrial fission, induced mitophagy, and aggravated inflammation in HG-treated ECs, while NCur reversed these changes. Also, HG and PM-induced endothelial inflammation is through the JNK signaling pathway and miR-221/222 specifically targeting ICAM-1 and BNIP3. PM exposure also aggravated mitochondrial ROS levels, mitochondrial fission, mitophagy, and endothelial inflammation in STZ-induced hyperglycemic mice, whereas NCur attenuated these changes.

Conclusion: This study elucidated the mechanisms underlying HG and PM-induced endothelial inflammation in vitro and in vivo. HG and PM treatment increased mitochondrial ROS, mitochondrial fission, and mitophagy in ECs, whereas NCur reversed these conditions. In addition, miR-221/222 plays a role in the amelioration of endothelial inflammation through targeting Bnip3 and ICAM-1, and NCur pretreatment can modulate miR-221/222 levels. Therefore, NCur may be a promising approach to intervene in diabetes and air pollution-induced CVD.

Keywords: endothelial inflammation; high glucose; miR-221/222; mitochondrial fission; nanocurcumin; particulate matter.

MeSH terms

  • Animals
  • Cardiovascular Diseases* / metabolism
  • Diabetes Mellitus* / metabolism
  • Endothelial Cells
  • Glucose / metabolism
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mitochondria / metabolism
  • Particulate Matter / toxicity
  • Reactive Oxygen Species / metabolism

Substances

  • Intercellular Adhesion Molecule-1
  • Particulate Matter
  • Reactive Oxygen Species
  • MicroRNAs
  • Glucose

Grants and funding

This work was supported by research grants from the National Science and Technology Council (MOST 108-2320-B-002-065-MY3; MOST 111-2320-B-002-022-MY3 to Y.L.C, and NSTC 112-2320-B-005-003- to T.C.L), the National Taiwan University Hospital (111-S0169; 112S0182 to J.S.T), and Partially supported by the iECG and Animal Biotechnology Center from the Feature Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE-111-S-0023-A) in Taiwan (T.C.L), and Chang Gung University of Science Foundation (Grant No. ZRRPF6M0011 to C.W.L).