Physiological shear stress suppresses apoptosis in human pulmonary microvascular endothelial cells
Abstract Physiological shear stress contributes to maintaining endothelial cell homeostasis, including suppression of apoptosis. In the pulmonary circulation, diseases such as pulmonary embolism and pulmonary hypertension result in alterations in shear stress. Shear stress has been reported to suppr...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.70269 |
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| author | Simin Yan Nicolas M. Philip Samuel T. Murray Xin Yun Michael P. Croglio Karthik Suresh Mahendra Damarla Larissa A. Shimoda Todd M. Kolb |
| author_facet | Simin Yan Nicolas M. Philip Samuel T. Murray Xin Yun Michael P. Croglio Karthik Suresh Mahendra Damarla Larissa A. Shimoda Todd M. Kolb |
| author_sort | Simin Yan |
| collection | DOAJ |
| description | Abstract Physiological shear stress contributes to maintaining endothelial cell homeostasis, including suppression of apoptosis. In the pulmonary circulation, diseases such as pulmonary embolism and pulmonary hypertension result in alterations in shear stress. Shear stress has been reported to suppress endothelial apoptosis through phosphatidylinositol 3‐kinase (PI3K) activation, but evidence from human pulmonary microvascular endothelial cells (PMVECs) is lacking. We hypothesized that physiological shear stress activates PI3K to reduce apoptosis in human PMVECs. We utilized the orbital shaker model of shear stress to test our hypothesis. Apoptosis was evaluated by measuring chromatin condensation, caspase 3/7 activity, and DNA fragmentation. We found that shear stress caused a rapid and sustained increase in protein kinase B (Akt) phosphorylation, a surrogate for activated PI3K, in human PMVECs. Under static conditions, PI3K inhibition with LY294002 or challenge with the kinase inhibitor staurosporine (STS) induced apoptosis in PMVECs. Following exposure to shear stress for 24 h, LY294002‐ and STS‐induced apoptosis was reduced. The anti‐apoptotic effect of shear stress in STS‐challenged cells was reversed by PI3K inhibition. We conclude that physiological shear stress increases PI3K/Akt activity and suppresses apoptosis in normal human PMVECs. |
| format | Article |
| id | doaj-art-58ed97d54c344fa4987ff2c0ee5b03e8 |
| institution | Kabale University |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-58ed97d54c344fa4987ff2c0ee5b03e82025-08-20T03:40:54ZengWileyPhysiological Reports2051-817X2025-03-01136n/an/a10.14814/phy2.70269Physiological shear stress suppresses apoptosis in human pulmonary microvascular endothelial cellsSimin Yan0Nicolas M. Philip1Samuel T. Murray2Xin Yun3Michael P. Croglio4Karthik Suresh5Mahendra Damarla6Larissa A. Shimoda7Todd M. Kolb8Division of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADivision of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADivision of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADivision of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADivision of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADivision of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADivision of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADivision of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland USADivision of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland USAAbstract Physiological shear stress contributes to maintaining endothelial cell homeostasis, including suppression of apoptosis. In the pulmonary circulation, diseases such as pulmonary embolism and pulmonary hypertension result in alterations in shear stress. Shear stress has been reported to suppress endothelial apoptosis through phosphatidylinositol 3‐kinase (PI3K) activation, but evidence from human pulmonary microvascular endothelial cells (PMVECs) is lacking. We hypothesized that physiological shear stress activates PI3K to reduce apoptosis in human PMVECs. We utilized the orbital shaker model of shear stress to test our hypothesis. Apoptosis was evaluated by measuring chromatin condensation, caspase 3/7 activity, and DNA fragmentation. We found that shear stress caused a rapid and sustained increase in protein kinase B (Akt) phosphorylation, a surrogate for activated PI3K, in human PMVECs. Under static conditions, PI3K inhibition with LY294002 or challenge with the kinase inhibitor staurosporine (STS) induced apoptosis in PMVECs. Following exposure to shear stress for 24 h, LY294002‐ and STS‐induced apoptosis was reduced. The anti‐apoptotic effect of shear stress in STS‐challenged cells was reversed by PI3K inhibition. We conclude that physiological shear stress increases PI3K/Akt activity and suppresses apoptosis in normal human PMVECs.https://doi.org/10.14814/phy2.70269apoptosishuman pulmonary microvascular endothelial cellsphosphatidylinositol 3‐kinaseshear stress |
| spellingShingle | Simin Yan Nicolas M. Philip Samuel T. Murray Xin Yun Michael P. Croglio Karthik Suresh Mahendra Damarla Larissa A. Shimoda Todd M. Kolb Physiological shear stress suppresses apoptosis in human pulmonary microvascular endothelial cells Physiological Reports apoptosis human pulmonary microvascular endothelial cells phosphatidylinositol 3‐kinase shear stress |
| title | Physiological shear stress suppresses apoptosis in human pulmonary microvascular endothelial cells |
| title_full | Physiological shear stress suppresses apoptosis in human pulmonary microvascular endothelial cells |
| title_fullStr | Physiological shear stress suppresses apoptosis in human pulmonary microvascular endothelial cells |
| title_full_unstemmed | Physiological shear stress suppresses apoptosis in human pulmonary microvascular endothelial cells |
| title_short | Physiological shear stress suppresses apoptosis in human pulmonary microvascular endothelial cells |
| title_sort | physiological shear stress suppresses apoptosis in human pulmonary microvascular endothelial cells |
| topic | apoptosis human pulmonary microvascular endothelial cells phosphatidylinositol 3‐kinase shear stress |
| url | https://doi.org/10.14814/phy2.70269 |
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