ArticleFrontiers in cardiovascular medicine2021
Antiretroviral Drugs Regulate Epigenetic Modification of Cardiac Cells Through Modulation of H3K9 and H3K27 Acetylation.
Article in Frontiers in cardiovascular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- HIV associated epigenetic trends and chronic diseases: insights into the hidden burden of chronic infection.Clinical epigenetics · 2026Review
- Post-translational acylation of proteins in cardiac hypertrophy.Nature reviews. Cardiology · 2025Review
- Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025Review
- HIV Protein Nef Induces Cardiomyopathy Through Induction of Bcl2 and p21.International journal of molecular sciences · 2024Article
- Valoctocogene roxaparvovec gene transfer in participants with HIV.Blood advances · 2023Article
- Direct and indirect cardiovascular and cardiometabolic sequelae of the combined anti-retroviral therapy on people living with HIV.Frontiers in physiology · 2023Review
- Eugenol attenuates ischemia-mediated oxidative stress in cardiomyocytes via acetylation of histone at H3K27.Free radical biology & medicine · 2023Article
- Development of innate immune memory by non-immune cells duringFrontiers in immunology · 2023Article
- Roles of histone acetylation sites in cardiac hypertrophy and heart failure.Frontiers in cardiovascular medicine · 2023Review
- HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy.Cells · 2021Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Antiretroviral therapy (ART) has significantly reduced the rate of mortality in HIV infected population, but people living with HIV (PLWH) show higher rates of cardiovascular disease (CVD). However, the effect of antiretroviral (ARV) drug treatment on cardiac cells is not clear. In this study, we explored the effect of ARV drugs in cardiomyocyte epigenetic remodeling. Primary cardiomyocytes were treated with a combination of four ARV drugs (ritonavir, abacavir, atazanavir, and lamivudine), and epigenetic changes were examined. Our data suggest that ARV drugs treatment significantly reduces acetylation at H3K9 and H3K27 and promotes methylation at H3K9 and H3K27, which are histone marks for gene expression activation and gene repression, respectively. Besides, ARV drugs treatment causes pathological changes in the cell through increased production of reactive oxygen species (ROS) and cellular hypertrophy. Further, the expression of chromatin remodeling enzymes was monitored in cardiomyocytes treated with ARV drugs using PCR array. The PCR array data indicated that the expression of epigenetic enzymes was differentially regulated in the ARV drugs treated cardiomyocytes. Consistent with the PCR array result, SIRT1, SUV39H1, and EZH2 protein expression was significantly upregulated in ARV drugs treated cardiomyocytes. Furthermore, gene expression analysis of the heart tissue from HIV+ patients showed that the expression of SIRT1, SUV39H1, and EZH2 was up-regulated in patients with a history of ART. Additionally, we found that expression of SIRT1 can protect cardiomyocytes in presence of ARV drugs through reduction of cellular ROS and cellular hypertrophy. Our results reveal that ARV drugs modulate the epigenetic histone markers involved in gene expression, and play a critical role in histone deacetylation at H3K9 and H3K27 during cellular stress. This study may lead to development of novel therapeutic strategies for the treatment of CVD in PLWH.
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