Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle
Arterial aging results in a progressive reduction in elasticity of the vessel wall and an impaired ability of aged blood vessels to control local blood flow and pressure. Recently, a new concept has emerged that the stiffness and decreased contractility of vascular smooth muscle (VSM) cells are impo...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.913673/full |
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| author | Krishna Raj Ojha Song Yi Shin Samuel Padgham Frida Leon Olmedo Bohong Guo Gang Han Christopher Woodman Andreea Trache Andreea Trache |
| author_facet | Krishna Raj Ojha Song Yi Shin Samuel Padgham Frida Leon Olmedo Bohong Guo Gang Han Christopher Woodman Andreea Trache Andreea Trache |
| author_sort | Krishna Raj Ojha |
| collection | DOAJ |
| description | Arterial aging results in a progressive reduction in elasticity of the vessel wall and an impaired ability of aged blood vessels to control local blood flow and pressure. Recently, a new concept has emerged that the stiffness and decreased contractility of vascular smooth muscle (VSM) cells are important contributors to age-induced arterial dysfunction. This study investigated the hypothesis that aging alters integrin function in a matrix stiffness-dependent manner, which contributes to decreased VSM contractility in aged soleus muscle feed arteries (SFA). The effect of RGD-binding integrins on contractile function of cannulated SFA isolated from young (4 months) and old (24 months) Fischer 344 rats was assessed by measuring constrictor responses to norepinephrine, phenylephrine, and angiotensin II. Results indicated that constrictor responses in presence of RGD were impaired in old compared to young SFA. VSM cells isolated from young and old SFA were used for functional experiments using atomic force microscopy and high-resolution imaging. Aging was associated with a modulation of integrin β1 recruitment at cell-matrix adhesions that was matrix and substrate stiffness dependent. Our data showed that substrate stiffening drives altered integrin β1 expression in aging, while soft substrates abolish age-induced differences in overall integrin β1 expression. In addition, substrate stiffness and matrix composition contribute to the modulation of SMα-actin cytoskeleton architecture with soft substrates reducing age effects. Our results provide new insights into age-induced structural changes at VSM cell level that translates to decreased functionality of aged resistance soleus feed arteries. |
| first_indexed | 2024-12-11T17:22:17Z |
| format | Article |
| id | doaj.art-f0743a6f5cbb42daa64f02e29099366b |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-11T17:22:17Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-f0743a6f5cbb42daa64f02e29099366b2022-12-22T00:57:05ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-07-011310.3389/fphys.2022.913673913673Age-Associated Dysregulation of Integrin Function in Vascular Smooth MuscleKrishna Raj Ojha0Song Yi Shin1Samuel Padgham2Frida Leon Olmedo3Bohong Guo4Gang Han5Christopher Woodman6Andreea Trache7Andreea Trache8Department of Medical Physiology, Texas A&M University Health Science Center, Bryan, TX, United StatesDepartment of Health and Kinesiology, Texas A&M University, College Station, TX, United StatesDepartment of Medical Physiology, Texas A&M University Health Science Center, Bryan, TX, United StatesDepartment of Biomedical Engineering, Texas A&M University, College Station, TX, United StatesDepartment of Epidemiology and Statistics, Texas A&M University Health Science Center, College Station, TX, United StatesDepartment of Epidemiology and Statistics, Texas A&M University Health Science Center, College Station, TX, United StatesDepartment of Health and Kinesiology, Texas A&M University, College Station, TX, United StatesDepartment of Medical Physiology, Texas A&M University Health Science Center, Bryan, TX, United StatesDepartment of Biomedical Engineering, Texas A&M University, College Station, TX, United StatesArterial aging results in a progressive reduction in elasticity of the vessel wall and an impaired ability of aged blood vessels to control local blood flow and pressure. Recently, a new concept has emerged that the stiffness and decreased contractility of vascular smooth muscle (VSM) cells are important contributors to age-induced arterial dysfunction. This study investigated the hypothesis that aging alters integrin function in a matrix stiffness-dependent manner, which contributes to decreased VSM contractility in aged soleus muscle feed arteries (SFA). The effect of RGD-binding integrins on contractile function of cannulated SFA isolated from young (4 months) and old (24 months) Fischer 344 rats was assessed by measuring constrictor responses to norepinephrine, phenylephrine, and angiotensin II. Results indicated that constrictor responses in presence of RGD were impaired in old compared to young SFA. VSM cells isolated from young and old SFA were used for functional experiments using atomic force microscopy and high-resolution imaging. Aging was associated with a modulation of integrin β1 recruitment at cell-matrix adhesions that was matrix and substrate stiffness dependent. Our data showed that substrate stiffening drives altered integrin β1 expression in aging, while soft substrates abolish age-induced differences in overall integrin β1 expression. In addition, substrate stiffness and matrix composition contribute to the modulation of SMα-actin cytoskeleton architecture with soft substrates reducing age effects. Our results provide new insights into age-induced structural changes at VSM cell level that translates to decreased functionality of aged resistance soleus feed arteries.https://www.frontiersin.org/articles/10.3389/fphys.2022.913673/fullagingintegrinsactinvascular smooth muscleatomic force microscopy |
| spellingShingle | Krishna Raj Ojha Song Yi Shin Samuel Padgham Frida Leon Olmedo Bohong Guo Gang Han Christopher Woodman Andreea Trache Andreea Trache Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle Frontiers in Physiology aging integrins actin vascular smooth muscle atomic force microscopy |
| title | Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle |
| title_full | Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle |
| title_fullStr | Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle |
| title_full_unstemmed | Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle |
| title_short | Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle |
| title_sort | age associated dysregulation of integrin function in vascular smooth muscle |
| topic | aging integrins actin vascular smooth muscle atomic force microscopy |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.913673/full |
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