PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea?
Obstructive sleep apnea is a chronic and prevalent condition that is associated with endothelial dysfunction, atherosclerosis, and imposes excess overall cardiovascular risk and mortality. Despite its high prevalence and the susceptibility of CVD patients to OSA-mediated stressors, OSA is still unde...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/10/5516 |
| _version_ | 1797499223961239552 |
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| author | Mohammad Badran David Gozal |
| author_facet | Mohammad Badran David Gozal |
| author_sort | Mohammad Badran |
| collection | DOAJ |
| description | Obstructive sleep apnea is a chronic and prevalent condition that is associated with endothelial dysfunction, atherosclerosis, and imposes excess overall cardiovascular risk and mortality. Despite its high prevalence and the susceptibility of CVD patients to OSA-mediated stressors, OSA is still under-recognized and untreated in cardiovascular practice. Moreover, conventional OSA treatments have yielded either controversial or disappointing results in terms of protection against CVD, prompting the need for the identification of additional mechanisms and associated adjuvant therapies. Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of tissue-type plasminogen activator (tPA) and urinary-type plasminogen activator (uPA), is a key regulator of fibrinolysis and cell migration. Indeed, elevated PAI-1 expression is associated with major cardiovascular adverse events that have been attributed to its antifibrinolytic activity. However, extensive evidence indicates that PAI-1 can induce endothelial dysfunction and atherosclerosis through complex interactions within the vasculature in an antifibrinolytic-independent matter. Elevated PAI-1 levels have been reported in OSA patients. However, the impact of PAI-1 on OSA-induced CVD has not been addressed to date. Here, we provide a comprehensive review on the mechanisms by which OSA and its most detrimental perturbation, intermittent hypoxia (IH), can enhance the transcription of PAI-1. We also propose causal pathways by which PAI-1 can promote atherosclerosis in OSA, thereby identifying PAI-1 as a potential therapeutic target in OSA-induced CVD. |
| first_indexed | 2024-03-10T03:44:24Z |
| format | Article |
| id | doaj.art-6022772974b64cdf8f8376c727959e4c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:44:24Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6022772974b64cdf8f8376c727959e4c2023-11-23T11:23:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310551610.3390/ijms23105516PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea?Mohammad Badran0David Gozal1Department of Child Health and Child Health Research Institute, School of Medicine, University of Missouri, 400 N Keene St, Suite 010, Columbia, MO 65201, USADepartment of Child Health and Child Health Research Institute, School of Medicine, University of Missouri, 400 N Keene St, Suite 010, Columbia, MO 65201, USAObstructive sleep apnea is a chronic and prevalent condition that is associated with endothelial dysfunction, atherosclerosis, and imposes excess overall cardiovascular risk and mortality. Despite its high prevalence and the susceptibility of CVD patients to OSA-mediated stressors, OSA is still under-recognized and untreated in cardiovascular practice. Moreover, conventional OSA treatments have yielded either controversial or disappointing results in terms of protection against CVD, prompting the need for the identification of additional mechanisms and associated adjuvant therapies. Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of tissue-type plasminogen activator (tPA) and urinary-type plasminogen activator (uPA), is a key regulator of fibrinolysis and cell migration. Indeed, elevated PAI-1 expression is associated with major cardiovascular adverse events that have been attributed to its antifibrinolytic activity. However, extensive evidence indicates that PAI-1 can induce endothelial dysfunction and atherosclerosis through complex interactions within the vasculature in an antifibrinolytic-independent matter. Elevated PAI-1 levels have been reported in OSA patients. However, the impact of PAI-1 on OSA-induced CVD has not been addressed to date. Here, we provide a comprehensive review on the mechanisms by which OSA and its most detrimental perturbation, intermittent hypoxia (IH), can enhance the transcription of PAI-1. We also propose causal pathways by which PAI-1 can promote atherosclerosis in OSA, thereby identifying PAI-1 as a potential therapeutic target in OSA-induced CVD.https://www.mdpi.com/1422-0067/23/10/5516obstructive sleep apneaintermittent hypoxiaplasminogen activator inhibitor-1endothelial dysfunctionatherosclerosis |
| spellingShingle | Mohammad Badran David Gozal PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea? International Journal of Molecular Sciences obstructive sleep apnea intermittent hypoxia plasminogen activator inhibitor-1 endothelial dysfunction atherosclerosis |
| title | PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea? |
| title_full | PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea? |
| title_fullStr | PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea? |
| title_full_unstemmed | PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea? |
| title_short | PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea? |
| title_sort | pai 1 a major player in the vascular dysfunction in obstructive sleep apnea |
| topic | obstructive sleep apnea intermittent hypoxia plasminogen activator inhibitor-1 endothelial dysfunction atherosclerosis |
| url | https://www.mdpi.com/1422-0067/23/10/5516 |
| work_keys_str_mv | AT mohammadbadran pai1amajorplayerinthevasculardysfunctioninobstructivesleepapnea AT davidgozal pai1amajorplayerinthevasculardysfunctioninobstructivesleepapnea |