Carbon monoxide releasing molecule-2 attenuates angiotensin II-induced IL-6/Jak2/Stat3-associated inflammation by inhibiting NADPH oxidase- and mitochondria-derived ROS in human aortic smooth muscle cells.

Autor: Hsu CY; Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan; Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan., Vo TTT; School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan., Lee CW; Department of Nursing, Division of Basic Medical Sciences, Chronic Diseases and Health Promotion Research Center and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Puzi City, Chiayi County, Taiwan; Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County, Taiwan; Department of Safety Health and Environmental Engineering, Ming Chi University of Technology, New Taipei City, Taiwan; College of Medicine, Chang Gung University, Guishan District, Taoyuan City, Taiwan., Chen YL; Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan., Lin WN; Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan., Cheng HC; School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan., Vo QC; Department of Dental Biomaterials Science, Dental Research Institute and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea., Lee IT; School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: itlee0128@tmu.edu.tw.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2022 Apr; Vol. 198, pp. 114978. Date of Electronic Publication: 2022 Feb 23.
DOI: 10.1016/j.bcp.2022.114978
Abstrakt: Abdominal aortic aneurysm (AAA) is a common inflammatory vascular disease. Angiotensin II (Ang II) involves in AAA progression by promoting the proliferation and migration of vascular smooth muscle cells, the degradation of extracellular matrices, and the generation of ROS to lead to vascular inflammation. Carbon monoxide releasing molecule-2 (CORM-2) is known to exert anti-inflammatory and antioxidant activities. However, it remains unclear whether CORM-2 can suppress Ang II-induced vascular inflammation to prevent AAA progression. Therefore, this study aimed to investigate the vasoprotective effects of CORM-2 against Ang II-induced inflammatory responses of human aortic smooth muscle cells (HASMCs) and the underlying mechanisms of those effects. The results showed that Ang II induced inflammatory responses of HASMCs via NADPH oxidase- and mitochondria-derived ROS/NF-κB/IL-6/Jak2/Stat3 pathway which was attenuated by the pretreatment with CORM-2. Additionally, CORM-2 further exhibited anti-inflammatory activities in Ang II-stimulated HASMCs, as indicated by the reduction of monocyte adhesion to HASMCs and migration of HASMCs via the suppression of ICAM-1 and VCAM-1 as well as MMP-2 and MMP-9 levels, respectively. Moreover, Ang II-induced COX-2-mediated PGE 2 secretion was also inhibited by the pretreatment with CORM-2. Importantly, our data demonstrated that CORM-2 reversed Ang II-induced IL-6 overexpression dependent on Nrf2 activation and HO-1 expression. Taken together, the present study indicates that CORM-2-induced Nrf2/HO-1 alleviates IL-6/Jak2/Stat3-mediated inflammatory responses to Ang II by inhibiting NADPH oxidase- and mitochondria-derived ROS, suggesting that CORM-2 is a promising pharmacologic candidate to reverse the pathological changes involved in the inflammation of vessel wall for the prevention and treatment of AAA.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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