Pulmonary Arterial Stiffness: An Early and Pervasive Driver of Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a historically neglected and highly morbid vascular disease that leads to right heart failure and, in some cases, death. The molecular origins of this disease have been poorly defined, and as such, current pulmonary vasodilator therapies do not cure or revers...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmed.2018.00204/full |
| _version_ | 1811301630549688320 |
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| author | Wei Sun Stephen Y. Chan |
| author_facet | Wei Sun Stephen Y. Chan |
| author_sort | Wei Sun |
| collection | DOAJ |
| description | Pulmonary arterial hypertension (PAH) is a historically neglected and highly morbid vascular disease that leads to right heart failure and, in some cases, death. The molecular origins of this disease have been poorly defined, and as such, current pulmonary vasodilator therapies do not cure or reverse this disease. Although extracellular matrix (ECM) remodeling and pulmonary arterial stiffening have long been associated with end-stage PAH, recent studies have reported that such vascular stiffening can occur early in pathogenesis. Furthermore, there is emerging evidence that ECM stiffening may represent a key first step in pathogenic reprogramming and molecular crosstalk among endothelial, smooth muscle, and fibroblast cells in the remodeled pulmonary vessel. Such processes represent the convergence of activation of a number of specific mechanoactivated signaling pathways, microRNAs, and metabolic pathways in pulmonary vasculature. In this review, we summarize the contemporary understanding of vascular stiffening as a driver of PAH, its mechanisms, potential therapeutic targets and clinical perspectives. Of note, early intervention targeting arterial stiffness may break the vicious cycle of PAH progression, leading to outcome improvement which has not been demonstrated by current vasodilator therapy. |
| first_indexed | 2024-04-13T07:12:24Z |
| format | Article |
| id | doaj.art-54767bf230bf4f5393da800dd73959d8 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-13T07:12:24Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-54767bf230bf4f5393da800dd73959d82022-12-22T02:56:50ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2018-07-01510.3389/fmed.2018.00204346843Pulmonary Arterial Stiffness: An Early and Pervasive Driver of Pulmonary Arterial HypertensionWei SunStephen Y. ChanPulmonary arterial hypertension (PAH) is a historically neglected and highly morbid vascular disease that leads to right heart failure and, in some cases, death. The molecular origins of this disease have been poorly defined, and as such, current pulmonary vasodilator therapies do not cure or reverse this disease. Although extracellular matrix (ECM) remodeling and pulmonary arterial stiffening have long been associated with end-stage PAH, recent studies have reported that such vascular stiffening can occur early in pathogenesis. Furthermore, there is emerging evidence that ECM stiffening may represent a key first step in pathogenic reprogramming and molecular crosstalk among endothelial, smooth muscle, and fibroblast cells in the remodeled pulmonary vessel. Such processes represent the convergence of activation of a number of specific mechanoactivated signaling pathways, microRNAs, and metabolic pathways in pulmonary vasculature. In this review, we summarize the contemporary understanding of vascular stiffening as a driver of PAH, its mechanisms, potential therapeutic targets and clinical perspectives. Of note, early intervention targeting arterial stiffness may break the vicious cycle of PAH progression, leading to outcome improvement which has not been demonstrated by current vasodilator therapy.https://www.frontiersin.org/article/10.3389/fmed.2018.00204/fullpulmonary arterial hypertensionarterial stiffnessendotheliumextracellular matrixvascular metabolism |
| spellingShingle | Wei Sun Stephen Y. Chan Pulmonary Arterial Stiffness: An Early and Pervasive Driver of Pulmonary Arterial Hypertension Frontiers in Medicine pulmonary arterial hypertension arterial stiffness endothelium extracellular matrix vascular metabolism |
| title | Pulmonary Arterial Stiffness: An Early and Pervasive Driver of Pulmonary Arterial Hypertension |
| title_full | Pulmonary Arterial Stiffness: An Early and Pervasive Driver of Pulmonary Arterial Hypertension |
| title_fullStr | Pulmonary Arterial Stiffness: An Early and Pervasive Driver of Pulmonary Arterial Hypertension |
| title_full_unstemmed | Pulmonary Arterial Stiffness: An Early and Pervasive Driver of Pulmonary Arterial Hypertension |
| title_short | Pulmonary Arterial Stiffness: An Early and Pervasive Driver of Pulmonary Arterial Hypertension |
| title_sort | pulmonary arterial stiffness an early and pervasive driver of pulmonary arterial hypertension |
| topic | pulmonary arterial hypertension arterial stiffness endothelium extracellular matrix vascular metabolism |
| url | https://www.frontiersin.org/article/10.3389/fmed.2018.00204/full |
| work_keys_str_mv | AT weisun pulmonaryarterialstiffnessanearlyandpervasivedriverofpulmonaryarterialhypertension AT stephenychan pulmonaryarterialstiffnessanearlyandpervasivedriverofpulmonaryarterialhypertension |