Date of Award

10-10-2024

Degree Type

Thesis

Degree Name

MPhil in Biological and Biomedical Sciences

First Advisor

Dr. Satwat Hashm

Second Advisor

Dr. Arooj Shafiq

Third Advisor

Dr. Mati-Ur-Rehman

Department

Biological and Biomedical Sciences

Abstract

Cardiovascular diseases (CVDs), particularly myocardial infarction (MI), are leading causes of morbidity and mortality worldwide with significant age- and sex-related differences in disease prevalence and outcomes. This study aimed to investigate the age- and sex-dependent molecular responses in murine models of MI, focusing on the renin-angiotensin-aldosterone system (RAAS) components, ROCK1 and ROCK2 expression, and associated markers (GFAP, vimentin, and desmin). Using BALB/C mice, we compared young and old male and female groups that underwent either sham surgery or MI induction. Troponin I levels were assessed as an indicator of myocardial injury, while the expression of ROCK1, ROCK2, GFAP, vimentin, and RAAS components was evaluated through immunohistochemistry and ELISA techniques. The results indicated that myocardial injury was more severe in older male mice, as evidenced by higher troponin I levels, whereas female mice showed no significant age-related differences in injury severity. ROCK1 expression was elevated across all MI groups, without significant age- or sex-specific variations. In contrast, ROCK2 expression showed a pronounced age-related increase in older female mice, suggesting a stronger role in cardiac remodeling for this group. GFAP expression was lower in older females, indicating an attenuated inflammatory response, while vimentin levels were significantly higher in older males, reflecting an enhanced fibrotic response. The RAAS analysis revealed a significant age-related increase in angiotensin II levels in males, with renin levels varying significantly across age and sex groups. In conclusion, this study demonstrates distinct age- and sex-related molecular responses to MI in mice, with older males exhibiting more severe cardiac injury, inflammation and fibrosis as seen by elevated troponin I, GFAP and vimentin levels and older females showing unique patterns in ROCK2, GFAP, and vimentin expression. These findings underscore the importance of considering age and sex in the development of targeted therapeutic strategies for MI, particularly in modulating ROCK 2 activity, RAAS signaling, and fibrotic processes. Further research is needed to explore these mechanisms and optimize treatment approaches for myocardial injury in different demographic groups

First Page

1

Last Page

88

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