Mechanical signaling regulates vascular smooth muscle cell adaptation in aging
Aging is an independent risk factor for cardiovascular disease. Preventing age-induced arterial dysfunction and the associated risk of cardiovascular disease remains a significant clinical challenge. Aerobic exercise, which induces a temporary increase in both blood flow and pressure in active tissu...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2025.1593886/full |
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| author | Amin Mohajeri Song Yi Shin Samuel Padgham Devon J. Boland Dana Pittman Ratterree Jacob Blizman Gang Han Christopher R. Woodman Andreea Trache Andreea Trache |
| author_facet | Amin Mohajeri Song Yi Shin Samuel Padgham Devon J. Boland Dana Pittman Ratterree Jacob Blizman Gang Han Christopher R. Woodman Andreea Trache Andreea Trache |
| author_sort | Amin Mohajeri |
| collection | DOAJ |
| description | Aging is an independent risk factor for cardiovascular disease. Preventing age-induced arterial dysfunction and the associated risk of cardiovascular disease remains a significant clinical challenge. Aerobic exercise, which induces a temporary increase in both blood flow and pressure in active tissue, has been shown to reduce macroscale arterial stiffening in humans. This study investigates the effects of mechanical stimuli on improving aging pathophysiology of vascular smooth muscle (VSM) cells isolated from soleus feed arteries (SFA). We hypothesized that age-induced impairment of VSM contractility can be rescued by mechanical stimulation that enhances formation of smooth muscle alpha-actin (SMα-actin) fibers and cell-matrix adhesions in aged VSM cells. Ex-vivo functional studies were used to assess myogenic contractility of VSM in isolated SFA from young (4 months) and old (24 months) Fischer 344 rats. These data indicated that pre-treatment of isolated aged SFA with a short-duration increase in intraluminal pressure rescued contractility. The mechanical stretch-induced remodeling of the cellular architecture was assessed in VSM cells isolated from young and old SFA. To dissect the mechanisms involved, the structural and functional properties of VSM cells were assessed by using mechanical stimulation combined with fluorescence confocal microscopy. Results showed that aged VSM cells respond faster than young cells to 2D biaxial cyclic stretch by increasing actin stress fiber formation and vinculin recruitment at cell-matrix adhesions. In addition, hydrostatic pressure treatment applied to aged VSM cells plated on stiffer substrates restored actin fibers and integrin β1 recruitment. Taken together, these findings suggest that discrete VSM cell mechanical properties and their ability to adapt to external mechanical signals are key in restoring VSM contractility in aging. These results are significant because they provide a novel understanding of the mechanisms by which mechanical stimulation improves VSM contractility in aged resistance arteries. Our results provide new insights into the role of VSM in vascular aging and highlight a new direction for mitigating age-related effects via mechanical stimulation-induced VSM remodeling. |
| format | Article |
| id | doaj-art-4f779f69c83f4eb59980b5e35ab67d6b |
| institution | DOAJ |
| issn | 1664-042X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj-art-4f779f69c83f4eb59980b5e35ab67d6b2025-08-20T03:11:39ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-07-011610.3389/fphys.2025.15938861593886Mechanical signaling regulates vascular smooth muscle cell adaptation in agingAmin Mohajeri0Song Yi Shin1Samuel Padgham2Devon J. Boland3Dana Pittman Ratterree4Jacob Blizman5Gang Han6Christopher R. Woodman7Andreea Trache8Andreea Trache9Department of Kinesiology and Sport Management, Texas A&M University, College Station, TX, United StatesDepartment of Kinesiology and Sport Management, Texas A&M University, College Station, TX, United StatesDepartment of Medical Physiology, Texas A&M University Health Science Center, Bryan, TX, United StatesTexas A&M Institute for Genome Sciences & Society, Texas A&M University, College Station, TX, United StatesDepartment of Epidemiology and Statistics, Texas A&M University School of Public Health, College Station, TX, United StatesDepartment of Biomedical Engineering, Texas A&M University, College Station, TX, United StatesDepartment of Epidemiology and Statistics, Texas A&M University School of Public Health, College Station, TX, United StatesDepartment of Kinesiology and Sport Management, 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 StatesAging is an independent risk factor for cardiovascular disease. Preventing age-induced arterial dysfunction and the associated risk of cardiovascular disease remains a significant clinical challenge. Aerobic exercise, which induces a temporary increase in both blood flow and pressure in active tissue, has been shown to reduce macroscale arterial stiffening in humans. This study investigates the effects of mechanical stimuli on improving aging pathophysiology of vascular smooth muscle (VSM) cells isolated from soleus feed arteries (SFA). We hypothesized that age-induced impairment of VSM contractility can be rescued by mechanical stimulation that enhances formation of smooth muscle alpha-actin (SMα-actin) fibers and cell-matrix adhesions in aged VSM cells. Ex-vivo functional studies were used to assess myogenic contractility of VSM in isolated SFA from young (4 months) and old (24 months) Fischer 344 rats. These data indicated that pre-treatment of isolated aged SFA with a short-duration increase in intraluminal pressure rescued contractility. The mechanical stretch-induced remodeling of the cellular architecture was assessed in VSM cells isolated from young and old SFA. To dissect the mechanisms involved, the structural and functional properties of VSM cells were assessed by using mechanical stimulation combined with fluorescence confocal microscopy. Results showed that aged VSM cells respond faster than young cells to 2D biaxial cyclic stretch by increasing actin stress fiber formation and vinculin recruitment at cell-matrix adhesions. In addition, hydrostatic pressure treatment applied to aged VSM cells plated on stiffer substrates restored actin fibers and integrin β1 recruitment. Taken together, these findings suggest that discrete VSM cell mechanical properties and their ability to adapt to external mechanical signals are key in restoring VSM contractility in aging. These results are significant because they provide a novel understanding of the mechanisms by which mechanical stimulation improves VSM contractility in aged resistance arteries. Our results provide new insights into the role of VSM in vascular aging and highlight a new direction for mitigating age-related effects via mechanical stimulation-induced VSM remodeling.https://www.frontiersin.org/articles/10.3389/fphys.2025.1593886/fullagingintegrinsactinmechanical stimulationvascular smooth muscle |
| spellingShingle | Amin Mohajeri Song Yi Shin Samuel Padgham Devon J. Boland Dana Pittman Ratterree Jacob Blizman Gang Han Christopher R. Woodman Andreea Trache Andreea Trache Mechanical signaling regulates vascular smooth muscle cell adaptation in aging Frontiers in Physiology aging integrins actin mechanical stimulation vascular smooth muscle |
| title | Mechanical signaling regulates vascular smooth muscle cell adaptation in aging |
| title_full | Mechanical signaling regulates vascular smooth muscle cell adaptation in aging |
| title_fullStr | Mechanical signaling regulates vascular smooth muscle cell adaptation in aging |
| title_full_unstemmed | Mechanical signaling regulates vascular smooth muscle cell adaptation in aging |
| title_short | Mechanical signaling regulates vascular smooth muscle cell adaptation in aging |
| title_sort | mechanical signaling regulates vascular smooth muscle cell adaptation in aging |
| topic | aging integrins actin mechanical stimulation vascular smooth muscle |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2025.1593886/full |
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