Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2023; 14(12): 1849-1861
Published online Dec 15, 2023. doi: 10.4239/wjd.v14.i12.1849
Atorvastatin ameliorated myocardial fibrosis in db/db mice by inhibiting oxidative stress and modulating macrophage polarization
Xian-Min Song, Meng-Nan Zhao, Gui-Zhi Li, Na Li, Ting Wang, Hong Zhou
Xian-Min Song, Meng-Nan Zhao, Gui-Zhi Li, Na Li, Ting Wang, Hong Zhou, Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Xian-Min Song, Department of Geriatrics, Handan Central Hospital, Handan 056001, Hebei Province, China
Author contributions: Zhou H designed the study and revised the manuscript; Song XM performed the experiments and drafted the manuscript; Zhao MN participated in data processing and revised the manuscript; Li GZ and Li N contributed to animal feeding; Wang T performed statistical analyses; and all authors contributed to the article and approved the submission of this manuscript.
Supported by the Health Commission of Hebei Province, No. 20220998.
Institutional animal care and use committee statement: All procedures were approved by the Animal Experimental Ethics Committee of the Second Hospital of Hebei Medical University and the Animal Health Care Guidelines to minimize animal suffering.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data will be made available on request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong Zhou, PhD, Chief Physician, Doctor, Department of Endocrinology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei Province, China. zhoubs2013@163.com
Received: September 15, 2023
Peer-review started: September 15, 2023
First decision: September 20, 2023
Revised: September 29, 2023
Accepted: October 23, 2023
Article in press: October 23, 2023
Published online: December 15, 2023
Processing time: 90 Days and 6.2 Hours
Abstract
BACKGROUND

People with diabetes mellitus (DM) suffer from multiple chronic complications due to sustained hyperglycemia, especially diabetic cardiomyopathy (DCM). Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling. Macrophages polarize to two distinct phenotypes: M1 and M2, and such plasticity in phenotypes provide macrophages various biological functions.

AIM

To investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms.

METHODS

DCM mouse models were established and randomly divided into DM, atorvastatin, and metformin groups. C57BL/6 mice were used as the control. Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues. The expression of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β),M1 macrophages (iNOS+), and M2 macrophages (CD206+) were demonstrated by immunohistochemistry and immunofluorescence staining. The levels of TGF-β1, IL-1β, and TNF-α were detected by ELISA and real-time quantitative polymerase chain reaction. Malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) ac-tivities were also measured.

RESULTS

Treatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardial fibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment. Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin; lowered the levels of TGF-β1, TNF-α and IL-1β in serum and myocardium; decreased the concentration of MDA and increased SOD activity in myocardium of db/db mice; inhibited M1 macrophages; and promoted M2 macrophages.

CONCLUSION

Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with the antioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulating macrophage polarization.

Keywords: Atorvastatin; Diabetic cardiomyopathy; Myocardial fibrosis; Macrophage polarization; Inflammation; Oxidative stress

Core Tip: The occurrence and development of diabetic cardiomyopathy are accompanied by a few pathological mechanisms. The present study showed that atorvastatin had antioxidant properties on diabetic hearts. Cardiac tissues include many resident macrophages. In high glucose conditions, macrophages can upregulate glucose uptake and utilization and enhance the production of inflammatory cytokines. Dysregulation of macrophages between M1 and M2 phenotypes causes excessive inflammation and cardiac injury. Our study suggests that administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with the antioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulating macrophage polarization.