Date of Award

9-2019

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Qian Chen, PhD

Second Advisor

Dawn Shell, PhD

Third Advisor

Charlotte Greene, PhD

Abstract

Autophagy is a housekeeping process used to remove damaged cytoplasmic constituents and protein aggregates. However, a debate persists on whether autophagy is beneficial or detrimental when an ischemic/reperfusion (I/R) insult occurs in the heart. This study tested the effects of autophagy enhancers (rapamycin and trehalose) and an autophagy inhibitor (3-methyladenine) on cardiac function and infarct size after global ischemia (30 minutes) and reperfusion (45 minutes) when given prior to ischemia (pre-treatment) or at the beginning of reperfusion (post-treatment). Rapamycin (25nM) pre-treatment and post-treatment significantly restored final left ventricular developed pressure (LVDP) to 75.4±9.1% and 60±5% of initial baseline respectively (both n=5, p<0.05), compared to control I/R group (n=9) that recovered to 35±5.5% of initial baseline. Likewise, trehalose (5mM) pre-treatment and post-treatment also significantly restored final LVDP to 61.4±3.7% (n=6) and 69.1±2.7% (n=5) of their initial baseline respectively, compared to control I/R group (p<0.05). However, 3-Methyladenine (1mM) pre-treatment (n=6) and post-treatment (n=5) showed similar reduction in final LVDP to 24.7±9.1% and 33.4±12.8 % of their initial baseline respectively, as the control I/R group. Moreover, infarction percentage was significantly reduced by rapamycin pre-treatment and post-treatment (14 ± 2.8% and 21.4 ± 5.3%, respectively; both p<0.05); and trehalose pre-treatment and post-treatment (19.2 ± 3% and 15.2% ± 3, respectively; both p<0.05), but not by 3-Methyladenine pre-treatment or post-treatment (26±2% and 28±4.1%, respectively) when compared to control I/R group (38.6±4.3%). The data suggests that autophagy enhancement before ischemia or at reperfusion reduces I/R injury.

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