Date of Award

10-22-2023

Degree Type

Thesis

Degree Name

MPhil in Biological and Biomedical Sciences

First Advisor

Dr. Satwat Hashmi

Second Advisor

Dr. Arooj Shafiq

Third Advisor

Dr. Romana Idress

Department

Biological and Biomedical Sciences

Abstract

Cardiovascular diseases are rampant worldwide encompassing a wide range of complications. Myocardial infarction being among the top is significantly linked to morbidity and mortality. Gender discrepancies have been observed in how myocardial infarction affect males and females.
Objectives: This study aims to analyze the extent of injury, apoptotic pathway, inflammation and estradiol hormone response across age and sex in mouse model of myocardial infarction. We also examined the differential activation of renin angiotensin aldosterone system (RAAS) in both the sexes.
Materials and Methods: Experimental myocardial infarction models were prepared by ligating the left anterior descending coronary artery and sample collection was done after 24 hours. Apoptosis was measured in the heart samples by estimating the expression of Poly (ADP-ribose) polymerase (PARP), and Pro caspase 3 through western blotting and Bcl-2 expressions were studied through immunohistochemistry. Extent of myocardial injury was estimated by measuring Troponin-I levels in the serum and myocardial inflammation through measuring Galectin 3 levels in the heart tissue. The Estrogen hormone response after myocardial infarction was measured by Estradiol estimation and RAAS activation by renin estimation through enzyme linked immunosorbent assay.
Our results showed that extent of injury was greater in older male mice group as compared to older female mice group and young male group, with Troponin-I levels of old male mice (1811.1±444.2) pg/ml vs old female mice (1309.3±410.9) pg/ml, the difference was not statistically significant. Troponin-I levels of old male mice (1811.1± 444.2) pg/ml vs young male mice (982.8±174.0) pg/ml with a p value (0.002) statistically significant. Inflammation, reported as Galectin-3 levels, was significantly greater in old male mice group (96.2±12.1) pg/mg vs young male mice group (72.8±4.2) with a p value (0.04), there was no significant difference found between male old mice group (96.2±12.1) pg/mg vs female old mice group (85.5±7.4) pg/mg and the difference did not reach statistical significance. There was no significant difference in the apoptotic markers across age and sex in our experimental myocardial infarction groups. Estradiol hormone concentrations in female young sham mice and female young MI mice (86.2±2.9 vs 89.6±8.6) pg/ml with a p value (0.1) lies closer to each other however female old MI mice group showed increase in estradiol concentration (85.4±4.7 pg/ml) as compared to female old sham mice group (64.4±6.3), the difference did not reach statistical significance. Our results also show different patterns of RAAS activation after myocardial infarction in male and female groups. Renin levels are significantly higher in male young mice as compared to old male mice (36526.5±7069.7 pg/ml vs 13858.8±4693.1 pg/ml) with a p value (0.02), statistically significant. Old female mice group also showed significant rise in renin levels (34453.7±12101.8 pg/ml) as compared to old male mice group (13858.8±4693.1 pg/ml) with a p-value (0.03).
Conclusion: Older male mice show significantly greater myocardial injury at 24-hour post myocardial infarction time point which can be attributed to increased inflammation observed in this group. Other comparative groups showed slight differences in the values but are not statistically significant for extent of injury and inflammation both. No significant differences were observed in apoptotic markers among any of the groups. No striking differences found in estradiol concentrations across age and sex in female groups. The different pattern of RAAS activation in both sexes after myocardial infarction needs further investigation to unveil the mechanistic link.

First Page

1

Last Page

92

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