DNA Damage and Repair in Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a complex multifactorial disease with both genetic and environmental dynamics contributing to disease progression. Over the last decade, several studies have demonstrated the presence of genomic instability and increased levels of DNA damage in PAH lung vascu...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
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| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/11/10/1224 |
| _version_ | 1797550514313887744 |
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| author | Samantha Sharma Micheala A. Aldred |
| author_facet | Samantha Sharma Micheala A. Aldred |
| author_sort | Samantha Sharma |
| collection | DOAJ |
| description | Pulmonary arterial hypertension (PAH) is a complex multifactorial disease with both genetic and environmental dynamics contributing to disease progression. Over the last decade, several studies have demonstrated the presence of genomic instability and increased levels of DNA damage in PAH lung vascular cells, which contribute to their pathogenic apoptosis-resistant and proliferating characteristics. In addition, the dysregulated DNA damage response pathways have been indicated as causal factors for the presence of persistent DNA damage. To understand the significant implications of DNA damage and repair in PAH pathogenesis, the current review summarizes the recent advances made in this field. This includes an overview of the observed DNA damage in the nuclear and mitochondrial genome of PAH patients. Next, the irregularities observed in various DNA damage response pathways and their role in accumulating DNA damage, escaping apoptosis, and proliferation under a DNA damaging environment are discussed. Although the current literature establishes the pertinence of DNA damage in PAH, additional studies are required to understand the temporal sequence of the above-mentioned events. Further, an exploration of different types of DNA damage in conjunction with associated impaired DNA damage response in PAH will potentially stimulate early diagnosis of the disease and development of novel therapeutic strategies. |
| first_indexed | 2024-03-10T15:30:24Z |
| format | Article |
| id | doaj.art-46b4f0ab878848c299914eec03d10708 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T15:30:24Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-46b4f0ab878848c299914eec03d107082023-11-20T17:40:27ZengMDPI AGGenes2073-44252020-10-011110122410.3390/genes11101224DNA Damage and Repair in Pulmonary Arterial HypertensionSamantha Sharma0Micheala A. Aldred1Division of Pulmonary, Critical Care, Sleep & Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USADivision of Pulmonary, Critical Care, Sleep & Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USAPulmonary arterial hypertension (PAH) is a complex multifactorial disease with both genetic and environmental dynamics contributing to disease progression. Over the last decade, several studies have demonstrated the presence of genomic instability and increased levels of DNA damage in PAH lung vascular cells, which contribute to their pathogenic apoptosis-resistant and proliferating characteristics. In addition, the dysregulated DNA damage response pathways have been indicated as causal factors for the presence of persistent DNA damage. To understand the significant implications of DNA damage and repair in PAH pathogenesis, the current review summarizes the recent advances made in this field. This includes an overview of the observed DNA damage in the nuclear and mitochondrial genome of PAH patients. Next, the irregularities observed in various DNA damage response pathways and their role in accumulating DNA damage, escaping apoptosis, and proliferation under a DNA damaging environment are discussed. Although the current literature establishes the pertinence of DNA damage in PAH, additional studies are required to understand the temporal sequence of the above-mentioned events. Further, an exploration of different types of DNA damage in conjunction with associated impaired DNA damage response in PAH will potentially stimulate early diagnosis of the disease and development of novel therapeutic strategies.https://www.mdpi.com/2073-4425/11/10/1224pulmonary arterial hypertensionendothelial cellssmooth muscle cellsDNA damageDNA repair |
| spellingShingle | Samantha Sharma Micheala A. Aldred DNA Damage and Repair in Pulmonary Arterial Hypertension Genes pulmonary arterial hypertension endothelial cells smooth muscle cells DNA damage DNA repair |
| title | DNA Damage and Repair in Pulmonary Arterial Hypertension |
| title_full | DNA Damage and Repair in Pulmonary Arterial Hypertension |
| title_fullStr | DNA Damage and Repair in Pulmonary Arterial Hypertension |
| title_full_unstemmed | DNA Damage and Repair in Pulmonary Arterial Hypertension |
| title_short | DNA Damage and Repair in Pulmonary Arterial Hypertension |
| title_sort | dna damage and repair in pulmonary arterial hypertension |
| topic | pulmonary arterial hypertension endothelial cells smooth muscle cells DNA damage DNA repair |
| url | https://www.mdpi.com/2073-4425/11/10/1224 |
| work_keys_str_mv | AT samanthasharma dnadamageandrepairinpulmonaryarterialhypertension AT michealaaaldred dnadamageandrepairinpulmonaryarterialhypertension |