Atorvastatin ameliorated myocardial fibrosis in db/db mice by inhibiting oxidative stress and modulating macrophage polarization

ARTICLE HIGHLIGHTS

Research background

Statins were initially used to lower blood lipids; however, in addition to their lipid-lowering effects, statins are involved in the regulation of the inflammatory response and play an important role in cardiovascular protection. Macrophage polarization is involved in a variety of pathological processes. Macrophage polarization is likewise involved in the development of diabetic cardiomyopathy (DCM).

Research motivation

DCM is one of the serious complications of diabetes mellitus, and we wanted to explore whether atorvastatin could mitigate the effects on DCM by affecting macrophage polarization to reduce oxidative stress, inflammation, and cardiac fibrosis.

Research objectives

We used db/db mice as a type 2 diabetes model and randomly divided into three groups: The db/db mice received daily oral gavage of sterilized water group, atorvastatin group and metformin group. C56BL/6 mice were used as the control group.

Research methods

Cardiac function was evaluated by echocardiography. Histological evaluations are hematoxylin and eosin staining, Masson staining, immunohistochemistry, and immunofluorescence. ELISA and real-time quantitative polymerase chain reaction were also used.

Research results

Treatment with atorvastatin improved cardiac dysfunction in db/db mice. Atorvastatin reduced the levels of serum myocardial injury markers; lowered the levels of Inflammatory cytokines in serum and myocardium; decreased indicators of oxidative stress in myocardium of db/db mice; inhibited M1 macrophages and promoted M2 macrophages.

Research conclusions

Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated through modulating macrophage polarization.

Research perspectives

Our study further confirms the protective role of statins in cardiovascular disease and provides a new therapeutic target for DCM.