Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction
Sigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we character...
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| Format: | Article |
| Langue: | English |
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Frontiers Media S.A.
2024-04-01
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| Collection: | Frontiers in Physiology |
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| Accès en ligne: | https://www.frontiersin.org/articles/10.3389/fphys.2024.1386296/full |
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| author | Naznin Sultana Remex Chowdhury S. Abdullah Richa Aishwarya Gopi K. Kolluru James Traylor Mohammad Alfrad Nobel Bhuiyan Christopher G. Kevil Christopher G. Kevil A. Wayne Orr A. Wayne Orr Oren Rom Oren Rom Christopher B. Pattillo Md. Shenuarin Bhuiyan Md. Shenuarin Bhuiyan |
| author_facet | Naznin Sultana Remex Chowdhury S. Abdullah Richa Aishwarya Gopi K. Kolluru James Traylor Mohammad Alfrad Nobel Bhuiyan Christopher G. Kevil Christopher G. Kevil A. Wayne Orr A. Wayne Orr Oren Rom Oren Rom Christopher B. Pattillo Md. Shenuarin Bhuiyan Md. Shenuarin Bhuiyan |
| author_sort | Naznin Sultana Remex |
| collection | DOAJ |
| description | Sigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we characterized the expression of Sigmar1 in the vascular wall and assessed its physiological function in the vascular system using global Sigmar1 knockout (Sigmar1−/−) mice. We determined the expression of Sigmar1 in the vascular tissue using immunostaining and biochemical experiments in both human and mouse blood vessels. Deletion of Sigmar1 globally in mice (Sigmar1−/−) led to blood vessel wall reorganizations characterized by nuclei disarray of vascular smooth muscle cells, altered organizations of elastic lamina, and higher collagen fibers deposition in and around the arteries compared to wildtype littermate controls (Wt). Vascular function was assessed in mice using non-invasive time-transit method of aortic stiffness measurement and flow-mediated dilation (FMD) of the left femoral artery. Sigmar1−/− mice showed a notable increase in arterial stiffness in the abdominal aorta and failed to increase the vessel diameter in response to reactive-hyperemia compared to Wt. This was consistent with reduced plasma and tissue nitric-oxide bioavailability (NOx) and decreased phosphorylation of endothelial nitric oxide synthase (eNOS) in the aorta of Sigmar1−/− mice. Ultrastructural analysis by transmission electron microscopy (TEM) of aorta sections showed accumulation of elongated shaped mitochondria in both vascular smooth muscle and endothelial cells of Sigmar1−/− mice. In accordance, decreased mitochondrial respirometry parameters were found in ex-vivo aortic rings from Sigmar1 deficient mice compared to Wt controls. These data indicate a potential role of Sigmar1 in maintaining vascular homeostasis. |
| first_indexed | 2025-03-22T03:28:09Z |
| format | Article |
| id | doaj.art-38c1e6be13ee4ee4a8ebb4f046d3393c |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2025-03-22T03:28:09Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-38c1e6be13ee4ee4a8ebb4f046d3393c2024-04-29T04:33:27ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2024-04-011510.3389/fphys.2024.13862961386296Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunctionNaznin Sultana Remex0Chowdhury S. Abdullah1Richa Aishwarya2Gopi K. Kolluru3James Traylor4Mohammad Alfrad Nobel Bhuiyan5Christopher G. Kevil6Christopher G. Kevil7A. Wayne Orr8A. Wayne Orr9Oren Rom10Oren Rom11Christopher B. Pattillo12Md. Shenuarin Bhuiyan13Md. Shenuarin Bhuiyan14Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, United StatesDepartment of Pathology and Translational Pathobiology, Louisiana State University Health, Shreveport, LA, United StatesDepartment of Pathology and Translational Pathobiology, Louisiana State University Health, Shreveport, LA, United StatesDepartment of Pathology and Translational Pathobiology, Louisiana State University Health, Shreveport, LA, United StatesDepartment of Pathology and Translational Pathobiology, Louisiana State University Health, Shreveport, LA, United StatesDepartment of Internal Medicine, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, United StatesDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, United StatesDepartment of Pathology and Translational Pathobiology, Louisiana State University Health, Shreveport, LA, United StatesDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, United StatesDepartment of Pathology and Translational Pathobiology, Louisiana State University Health, Shreveport, LA, United StatesDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, United StatesDepartment of Pathology and Translational Pathobiology, Louisiana State University Health, Shreveport, LA, United StatesDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, United StatesDepartment of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, United StatesDepartment of Pathology and Translational Pathobiology, Louisiana State University Health, Shreveport, LA, United StatesSigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we characterized the expression of Sigmar1 in the vascular wall and assessed its physiological function in the vascular system using global Sigmar1 knockout (Sigmar1−/−) mice. We determined the expression of Sigmar1 in the vascular tissue using immunostaining and biochemical experiments in both human and mouse blood vessels. Deletion of Sigmar1 globally in mice (Sigmar1−/−) led to blood vessel wall reorganizations characterized by nuclei disarray of vascular smooth muscle cells, altered organizations of elastic lamina, and higher collagen fibers deposition in and around the arteries compared to wildtype littermate controls (Wt). Vascular function was assessed in mice using non-invasive time-transit method of aortic stiffness measurement and flow-mediated dilation (FMD) of the left femoral artery. Sigmar1−/− mice showed a notable increase in arterial stiffness in the abdominal aorta and failed to increase the vessel diameter in response to reactive-hyperemia compared to Wt. This was consistent with reduced plasma and tissue nitric-oxide bioavailability (NOx) and decreased phosphorylation of endothelial nitric oxide synthase (eNOS) in the aorta of Sigmar1−/− mice. Ultrastructural analysis by transmission electron microscopy (TEM) of aorta sections showed accumulation of elongated shaped mitochondria in both vascular smooth muscle and endothelial cells of Sigmar1−/− mice. In accordance, decreased mitochondrial respirometry parameters were found in ex-vivo aortic rings from Sigmar1 deficient mice compared to Wt controls. These data indicate a potential role of Sigmar1 in maintaining vascular homeostasis.https://www.frontiersin.org/articles/10.3389/fphys.2024.1386296/fullSIGMAR1physiological functionvascular functionmitochondriaflow mediated dilatation (FMD) |
| spellingShingle | Naznin Sultana Remex Chowdhury S. Abdullah Richa Aishwarya Gopi K. Kolluru James Traylor Mohammad Alfrad Nobel Bhuiyan Christopher G. Kevil Christopher G. Kevil A. Wayne Orr A. Wayne Orr Oren Rom Oren Rom Christopher B. Pattillo Md. Shenuarin Bhuiyan Md. Shenuarin Bhuiyan Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction Frontiers in Physiology SIGMAR1 physiological function vascular function mitochondria flow mediated dilatation (FMD) |
| title | Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction |
| title_full | Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction |
| title_fullStr | Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction |
| title_full_unstemmed | Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction |
| title_short | Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction |
| title_sort | deletion of sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction |
| topic | SIGMAR1 physiological function vascular function mitochondria flow mediated dilatation (FMD) |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2024.1386296/full |
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