Cardiovascular diseases (CVDs) are the leading causes of death globally. Recent studies show that CVDs are one of the major causes of morbidity and mortality in people living with HIV/AIDS (PLWHA). HIV symptoms arise as our body tries to fight off the virus but as our immune system weakens as CD4 T cells are targeted. As these T cells diminish in quantity, it leaves the body susceptible to other infections, which is why ARV drug treatment is used. NRTIs are common drug treatments for these viruses as they inhibit the enzyme reverse transcriptase. Unfortunately, these NRTIs are known to cause dilated cardiomyopathy, while protease inhibitors are known to cause increased cardiovascular mortality and heart failure. Treatment of these side effects is crucial since millions of people are on these ARV drug treatments.
Therefore, we analyzed RNA sequencing data of neonatal ventricular cardiomyocytes treated with ARV's to determine the regulatory pathway of upregulated/downregulated genes associated with the ARV treatment. It was seen that many of the upregulated genes such as PSEN and PSENEN2 were mitophagy control genes, and most of the downregulated genes were from complexes I-IV of the oxidative phosphorylation chain. Based on the genomic data, we hypothesized that increasing the expression of these downregulated genes could potentially reduce mitochondrial dysfunction and bring back the functionality of the complexes. Research has shown that rapamycin treatment can potentially reduce the effects of mitochondrial dysfunction, and tests were conducted to see how much expression changed. Another indicator of mitochondrial dysfunction is the detection of ROS, and this project aims to see how rapamycin will affect the presence of these ROS.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:honorstheses-2524 |
| Date | 01 January 2023 |
| Creators | Patel, Raj |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Honors Undergraduate Theses |
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