Simvastatin Improves Myocardial Ischemia Reperfusion Injury through KLF-Regulated Alleviation of Inflammation.

Abstract

OBJECTIVE:

To clarify the protective effect of simvastatin on myocardial ischemia reperfusion injury (MIRI) and the underlying mechanism.

MATERIALS AND METHODS:

The MIRI model in rats was firstly constructed. Twenty-four male rats were randomly assigned into the sham group, ischemia-reperfusion (I/R) group, and simvastatin group, with 8 rats in each group. Contents of superoxide dismutase (SOD) and malondialdehyde (MDA), as well as serum levels of CK and inflammatory factors, in rats were determined by the enzyme-linked immunosorbent assay (ELISA). Lactate dehydrogenase (LDH) activity in the three groups was examined. Through flow cytometry and Cell Counting Kit-8 (CCK-8) assay, apoptosis and viability in each group were detected, respectively. Relative levels of HMGB1, Kruppel-like factor 2 (KLF2), eNOS, and thrombomodulin (TM) were finally determined.

RESULTS:

Simvastatin treatment markedly enhanced SOD activity and reduced contents of MDA, LDH, and creatine kinase (CK) in MIRI rats. The increased apoptosis and decreased viability following MIRI were partially reversed by simvastatin treatment. Besides, MIRI resulted in the upregulation of inflammatory factors and chemokines. Their elevations were abolished by simvastatin. In MIRI rats, simvastatin upregulated KLF2 and p-eNOS.

CONCLUSIONS:

Simvastatin protects inflammatory response at post-MIRI through upregulating KLF2, thus improving cardiac function.

• Authors: Tingju Wei, Jun Li, Guowei Fu, Hui Zhao, Chen Huang, Xiaohua Zhu, Gongcheng Huang, Jing Xu
• Journal: Disease markers (Dis Markers) Vol. 2022 Pg. 7878602 ( 2022) ISSN: 1875-8630 [Electronic] United States
• PMID: 35059045 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Tingju Wei et al.

Chemical References

• Klf2 protein, rat
• Kruppel-Like Transcription Factors
• Simvastatin

Topics

• Animals
• Apoptosis
• Inflammation (drug therapy)
• Kruppel-Like Transcription Factors (genetics)
• Male
• Myocardial Reperfusion Injury (drug therapy)
• Rats
• Simvastatin (pharmacology, therapeutic use)