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

Abstract

Tsai-Chun Lai,1– 3 Chiang-Wen Lee,4– 6 Mei-Hsiang Hsu,1 Yu-Chen Chen,1,7 Shu-Rung Lin,8,9 Shu-Wha Lin,10 Tzu-Lin Lee,1 Shin-Yu Lin,11,12 Shu-Hao Hsu,1 Jaw-Shiun Tsai,13,14 Yuh-Lien Chen1 1Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; 2Department of Life Sciences, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan, Republic of China; 3The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung, Taiwan, Republic of China; 4Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County, Taiwan, Republic of China; 5Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City, Chiayi County, Taiwan, Republic of China; 6Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan City, Taiwan, Republic of China; 7Department of Medicine, Mackay Medical College, New Taipei City, Taiwan, Republic of China; 8Department of Bioscience Technology, College of Science, Chung-Yuan Christian University, Taoyuan, Taiwan, Republic of China; 9Center for Nanotechnology and Center for Biomedical Technology, Chung-Yuan Christian University, Taoyuan, Taiwan, Republic of China; 10Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; 11Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan; 12Department of Obstetrics and Gynecology, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China; 13Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China; 14Center for Complementary and Integrated Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of ChinaCorrespondence: Yuh-Lien Chen, Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen Ai Road, Taipei, 10051, Taiwan, Republic of China, Tel [phone]-288176, Fax [phone], Email [email protected] Jaw-Shiun Tsai, Department of Family Medicine, National Taiwan University Hospital, No. 1, Changde Street, Taipei, 10048, Taiwan, Republic of China, Tel [phone]-265147, Fax [phone], Email [email protected]: 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: particulate matter, high glucose, mitochondrial fission, endothelial inflammation, miR-221/222, nanocurcumin

Keywords

• particulate matter
• high glucose
• mitochondrial fission
• endothelial inflammation
• mir-221/222
• nanocurcumin.