Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation
Arterial stiffness, which increases with aging and hypertension, is an independent cardiovascular risk factor. While stiffer substrates are known to affect single endothelial cell morphology and migration, the effect of substrate stiffness on endothelial monolayer function is less understood. The ob...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Applied Bionics and Biomechanics |
| Online Access: | http://dx.doi.org/10.1155/2019/6578492 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841524792343134208 |
|---|---|
| author | Rebecca Lownes Urbano Swathi Swaminathan Alisa Morss Clyne |
| author_facet | Rebecca Lownes Urbano Swathi Swaminathan Alisa Morss Clyne |
| author_sort | Rebecca Lownes Urbano |
| collection | DOAJ |
| description | Arterial stiffness, which increases with aging and hypertension, is an independent cardiovascular risk factor. While stiffer substrates are known to affect single endothelial cell morphology and migration, the effect of substrate stiffness on endothelial monolayer function is less understood. The objective of this study was to determine if substrate stiffness increased endothelial monolayer reactive oxygen species (ROS) in response to protein kinase C (PKC) activation and if this oxidative stress then impacted adherens junction integrity. Porcine aortic endothelial cells were cultured on varied stiffness polyacrylamide gels and treated with phorbol 12-myristate 13-acetate (PMA), which stimulates PKC and ROS without increasing actinomyosin contractility. PMA-treated endothelial cells on stiffer substrates increased ROS and adherens junction loss without increased contractility. ROS scavengers abrogated PMA effects on cell-cell junctions, with a more profound effect in cells on stiffer substrates. Finally, endothelial cells in aortae from elastin haploinsufficient mice (Eln+/-), which were stiffer than aortae from wild-type mice, showed decreased VE-cadherin colocalization with peripheral actin following PMA treatment. These data suggest that oxidative stress may be enhanced in endothelial cells in stiffer vessels, which could contribute to the association between arterial stiffness and cardiovascular disease. |
| format | Article |
| id | doaj-art-96184c7f8fa14c01bf79ec552c71bb6a |
| institution | Kabale University |
| issn | 1176-2322 1754-2103 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Applied Bionics and Biomechanics |
| spelling | doaj-art-96184c7f8fa14c01bf79ec552c71bb6a2025-02-03T05:47:26ZengWileyApplied Bionics and Biomechanics1176-23221754-21032019-01-01201910.1155/2019/65784926578492Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C ActivationRebecca Lownes Urbano0Swathi Swaminathan1Alisa Morss Clyne2Mechanical Engineering and Mechanics, Drexel University, Philadelphia, PA, USABiomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USAMechanical Engineering and Mechanics, Drexel University, Philadelphia, PA, USAArterial stiffness, which increases with aging and hypertension, is an independent cardiovascular risk factor. While stiffer substrates are known to affect single endothelial cell morphology and migration, the effect of substrate stiffness on endothelial monolayer function is less understood. The objective of this study was to determine if substrate stiffness increased endothelial monolayer reactive oxygen species (ROS) in response to protein kinase C (PKC) activation and if this oxidative stress then impacted adherens junction integrity. Porcine aortic endothelial cells were cultured on varied stiffness polyacrylamide gels and treated with phorbol 12-myristate 13-acetate (PMA), which stimulates PKC and ROS without increasing actinomyosin contractility. PMA-treated endothelial cells on stiffer substrates increased ROS and adherens junction loss without increased contractility. ROS scavengers abrogated PMA effects on cell-cell junctions, with a more profound effect in cells on stiffer substrates. Finally, endothelial cells in aortae from elastin haploinsufficient mice (Eln+/-), which were stiffer than aortae from wild-type mice, showed decreased VE-cadherin colocalization with peripheral actin following PMA treatment. These data suggest that oxidative stress may be enhanced in endothelial cells in stiffer vessels, which could contribute to the association between arterial stiffness and cardiovascular disease.http://dx.doi.org/10.1155/2019/6578492 |
| spellingShingle | Rebecca Lownes Urbano Swathi Swaminathan Alisa Morss Clyne Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation Applied Bionics and Biomechanics |
| title | Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation |
| title_full | Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation |
| title_fullStr | Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation |
| title_full_unstemmed | Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation |
| title_short | Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation |
| title_sort | stiff substrates enhance endothelial oxidative stress in response to protein kinase c activation |
| url | http://dx.doi.org/10.1155/2019/6578492 |
| work_keys_str_mv | AT rebeccalownesurbano stiffsubstratesenhanceendothelialoxidativestressinresponsetoproteinkinasecactivation AT swathiswaminathan stiffsubstratesenhanceendothelialoxidativestressinresponsetoproteinkinasecactivation AT alisamorssclyne stiffsubstratesenhanceendothelialoxidativestressinresponsetoproteinkinasecactivation |