2. Academic Validation
  3. Bioinformatics and experimental studies jointly reveal that Sacubitril Valsartan improves myocardial oxidative stress and inflammation by regulating the MAPK signaling pathway to treat chemotherapy related cardiotoxicity

Bioinformatics and experimental studies jointly reveal that Sacubitril Valsartan improves myocardial oxidative stress and inflammation by regulating the MAPK signaling pathway to treat chemotherapy related cardiotoxicity

  • Biochem Biophys Res Commun. 2024 Jan 1:690:149244. doi: 10.1016/j.bbrc.2023.149244.
Hongwei Shi 1,  Hao Lu 2,  Yanlei Zheng 3,  Peng Pu 2,  Lai Wei 4,  Desheng Hu 5,  Heng Tang 6,  Linlin Wang 7
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 3 Department of Critical Care Medicine, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430079, China.
  • 4 Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
  • 6 Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Cardiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. Electronic address: [email protected].
  • 7 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
PMID: 38029488 DOI: 10.1016/j.bbrc.2023.149244
Abstract

Background: CRC is a common but serious complication or sequela of tumor treatment, and new coping strategies are urgently needed. SV is a classic clinical cardiovascular protective drug, which has been widely used in the treatment of heart failure, hypertension and Other Diseases. It has good therapeutic effect in Other cardiovascular diseases such as diabetes cardiomyopathy, ischemic cardiomyopathy and vascular disease, but it has not been proved by research that SV can prevent and treat CRC.

Method: In this study, DOX was used to induce a rat CRC model and evaluate the therapeutic effect of SV on it. Subsequently, R software was applied to analyze the control group, SV group, and DOX group in databases GSE207283 and GSE22369, and to screen for common differentially expressed genes. Use the DAVID website for enrichment analysis and visualization. Use STRING website to analyze and visualize protein interaction networks of key genes. Finally, experimental verification was conducted on key genes.

Result: Our research results show that SV has a protective effect on DOX induced myocardial injury by alleviating Weight loss, increasing Ejection fraction, and reducing the level of biomarkers of myocardial injury. Meanwhile, SV can effectively alleviate the above abnormalities. Bioinformatics and KEGG pathway analysis showed significant enrichment of metabolic and MAPK signaling pathways, suggesting that they may be the main regulatory pathway for SV treatment of CRC. Subsequent studies have also confirmed that SV can inhibit DOX induced myocardial injury through the MAPK signaling pathway, and alleviate DOX induced oxidative stress and inflammatory states.

Conclusion: Our research indicates that SV is a potential drug for treating CRC and preliminarily elucidates its molecular mechanism of regulating the MAPK pathway to improve oxidative stress and inflammation.

Keywords

Cardiotoxicity; Doxorubicin; MAPK; Sacubitril Valsartan.

Figures
Products