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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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Detalles Bibliográficos
Autores principales: Badran, Mohammad, Gozal, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141273/
https://www.ncbi.nlm.nih.gov/pubmed/35628326
http://dx.doi.org/10.3390/ijms23105516
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author Badran, Mohammad
Gozal, David
author_facet Badran, Mohammad
Gozal, David
author_sort Badran, Mohammad
collection PubMed
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.
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spelling pubmed-91412732022-05-28 PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea? Badran, Mohammad Gozal, David Int J Mol Sci Review 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. MDPI 2022-05-15 /pmc/articles/PMC9141273/ /pubmed/35628326 http://dx.doi.org/10.3390/ijms23105516 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Badran, Mohammad
Gozal, David
PAI-1: A Major Player in the Vascular Dysfunction in Obstructive Sleep Apnea?
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 Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141273/
https://www.ncbi.nlm.nih.gov/pubmed/35628326
http://dx.doi.org/10.3390/ijms23105516
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