HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy
People living with HIV (PLWH) have to take an antiretroviral therapy (ART) for life and show noncommunicable illnesses such as chronic inflammation, immune activation, and multiorgan dysregulation. Recent studies suggest that long-term use of ART induces comorbid conditions and is one of the leading...
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MDPI AG
2021-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/12/3458 |
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| author | Shiridhar Kashyap Maryam Rabbani Isabela de Lima Olena Kondrachuk Raj Patel Mahnoush Sophia Shafiei Avni Mukker Aishwarya Rajakumar Manish Kumar Gupta |
| author_facet | Shiridhar Kashyap Maryam Rabbani Isabela de Lima Olena Kondrachuk Raj Patel Mahnoush Sophia Shafiei Avni Mukker Aishwarya Rajakumar Manish Kumar Gupta |
| author_sort | Shiridhar Kashyap |
| collection | DOAJ |
| description | People living with HIV (PLWH) have to take an antiretroviral therapy (ART) for life and show noncommunicable illnesses such as chronic inflammation, immune activation, and multiorgan dysregulation. Recent studies suggest that long-term use of ART induces comorbid conditions and is one of the leading causes of heart failure in PLWH. However, the molecular mechanism of antiretroviral drugs (ARVs) induced heart failure is unclear. To determine the mechanism of ARVs induced cardiac dysfunction, we performed global transcriptomic profiling of ARVs treated neonatal rat ventricular cardiomyocytes in culture. Differentially expressed genes were identified by RNA-sequencing. Our data show that ARVs treatment causes upregulation of several biological functions associated with cardiotoxicity, hypertrophy, and heart failure. Global gene expression data were validated in cardiac tissue isolated from HIV patients having a history of ART. Interestingly, we found that homeodomain-only protein homeobox (HOPX) expression was significantly increased in cardiomyocytes treated with ARVs and in the heart tissue of HIV patients. Furthermore, we found that HOPX plays a crucial role in ARVs mediated cellular hypertrophy. Mechanistically, we found that HOPX plays a critical role in epigenetic regulation, through deacetylation of histone, while the HDAC inhibitor, Trichostatin A, can restore the acetylation level of histone 3 in the presence of ARVs. |
| first_indexed | 2024-03-10T04:26:17Z |
| format | Article |
| id | doaj.art-e6ad043d749d482b9838484e399afdc1 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:26:17Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e6ad043d749d482b9838484e399afdc12023-11-23T07:38:03ZengMDPI AGCells2073-44092021-12-011012345810.3390/cells10123458HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac HypertrophyShiridhar Kashyap0Maryam Rabbani1Isabela de Lima2Olena Kondrachuk3Raj Patel4Mahnoush Sophia Shafiei5Avni Mukker6Aishwarya Rajakumar7Manish Kumar Gupta8Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USADivision of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USADivision of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USADivision of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USADivision of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USADivision of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USADivision of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USADivision of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USADivision of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USAPeople living with HIV (PLWH) have to take an antiretroviral therapy (ART) for life and show noncommunicable illnesses such as chronic inflammation, immune activation, and multiorgan dysregulation. Recent studies suggest that long-term use of ART induces comorbid conditions and is one of the leading causes of heart failure in PLWH. However, the molecular mechanism of antiretroviral drugs (ARVs) induced heart failure is unclear. To determine the mechanism of ARVs induced cardiac dysfunction, we performed global transcriptomic profiling of ARVs treated neonatal rat ventricular cardiomyocytes in culture. Differentially expressed genes were identified by RNA-sequencing. Our data show that ARVs treatment causes upregulation of several biological functions associated with cardiotoxicity, hypertrophy, and heart failure. Global gene expression data were validated in cardiac tissue isolated from HIV patients having a history of ART. Interestingly, we found that homeodomain-only protein homeobox (HOPX) expression was significantly increased in cardiomyocytes treated with ARVs and in the heart tissue of HIV patients. Furthermore, we found that HOPX plays a crucial role in ARVs mediated cellular hypertrophy. Mechanistically, we found that HOPX plays a critical role in epigenetic regulation, through deacetylation of histone, while the HDAC inhibitor, Trichostatin A, can restore the acetylation level of histone 3 in the presence of ARVs.https://www.mdpi.com/2073-4409/10/12/3458cardiomyocytesantiretroviral therapyhypertrophyHOPXepigeneticsHDAC inhibitor |
| spellingShingle | Shiridhar Kashyap Maryam Rabbani Isabela de Lima Olena Kondrachuk Raj Patel Mahnoush Sophia Shafiei Avni Mukker Aishwarya Rajakumar Manish Kumar Gupta HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy Cells cardiomyocytes antiretroviral therapy hypertrophy HOPX epigenetics HDAC inhibitor |
| title | HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy |
| title_full | HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy |
| title_fullStr | HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy |
| title_full_unstemmed | HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy |
| title_short | HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy |
| title_sort | hopx plays a critical role in antiretroviral drugs induced epigenetic modification and cardiac hypertrophy |
| topic | cardiomyocytes antiretroviral therapy hypertrophy HOPX epigenetics HDAC inhibitor |
| url | https://www.mdpi.com/2073-4409/10/12/3458 |
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