Date of Award

10-31-2022

Degree Type

Thesis

Degree Name

MPhil in Biological and Biomedical Sciences

First Advisor

Dr. Satwat Hashmi

Second Advisor

Dr. Bushra amin

Third Advisor

Dr. Mati-Ur-Rehman

Department

Biological and Biomedical Sciences

Abstract

Ischemic heart disease (IHD) is among the notorious cause of mortality and morbidity worldwide. Myocardial infarction (MI) and ischemia reperfusion injury (IR) are the most common manifestations of IHD. Wnt/beta-catenin signaling pathway is activated post MI and IR and there are conflicting reports in literature regarding its role in the post MI and IR sequel.
Objective: This study aims to analyze the role of the Wnt/beta-catenin pathway and apoptosis in post-MI/IR models of mice. It also examines the role of Wnt inhibitor (pyrvinium pamoate) on Wnt/beta-catenin pathway signaling and its role in apoptosis.
Methods and Results: Male BALB/c mice were pretreated with a WNT pathway inhibitor pyrvinium pamoate (PP). Experimental murine IR and MI models were developed, andsamples were collected after 1 week. Masson trichrome staining was apt to calculate the infarct size and expansion index. Immunohistochemistry, enzyme-linked immunosorbent assay and western blotting were employed to study the expression of beta-catenin and various biomarkers of apoptosis; Bax/Bcl2, Bcl-xL and cleaved caspase-3, in left ventricle heart samples. Our results show that Wnt/beta-catenin signaling is activated in 1 week post MI and IR groups as compared to sham operated animals. It was also seen that the PP treated group in both MI and IR mice had decreased infarct size and expansion index as compared to untreated MI and IR groups. Apoptotic markers were significantly increased in post MI hearts as compared to post IR hearts and PP treatment showed a significant reduction in the expression of apoptotic biomarkers in both post MI and IR hearts.
Conclusion: Pyrvinium Pamoate treatment decreased infarct size and expansion index in 1 week post MI and IR hearts. It also caused decrease in the expression of apoptosis markers in post MI and IR hearts. These observations suggest a cardioprotective role of pyrvinium pamoate in mice after MI and IR

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1

Last Page

72

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