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Updated: Feb 24, 2026
Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
Published on: February 15, 2022
Adaptation of mitochondrial expression and ATP production in dedifferentiating vascular smooth muscle cells
Celena Scheede-Bergdahl1,2, Andreas Bergdahl3
1a Department of Kinesiology & Physical Education, McGill University, Montreal, QC H2W 1S4, Canada.
Insights
Mitochondria play a key role in early atherosclerosis. Studies show altered mitochondrial function, specifically Complex I activity, is linked to vascular smooth muscle cell dedifferentiation in atherosclerosis development.
Area of Science:
- Cardiovascular Biology
- Mitochondrial Medicine
- Cellular Biology
Background:
- Atherosclerosis is a major cause of death globally.
- Mitochondria are increasingly recognized for their role in atherosclerosis.
- Early mechanisms of vascular smooth muscle cell (VSMC) dedifferentiation in atherosclerosis are not fully understood.
Purpose of the Study:
- To investigate the role of mitochondria in VSMC dedifferentiation.
- To elucidate early-phase mechanisms in atherosclerosis development.
Main Methods:
- Murine aortic organ culture in serum-free media.
- High-resolution respirometry for mitochondrial function assessment.
- Immunoblotting for VSMC phenotype proteins and mitochondrial density.
Main Results:
- Mitochondrial Complex I activity significantly upregulated during VSMC dedifferentiation.
- Diminished coupling between phosphorylation and oxidation observed, suggesting increased ADP:ATP ratio.
- Evidence of increased electron transport chain leak and altered mitochondrial function at Complex I.
Conclusions:
- Mitochondrial function, particularly Complex I, is altered during VSMC dedifferentiation.
- These changes are associated with the early stages of atherosclerosis.
- Mitochondrial alterations are integral to the VSMC phenotype switch in atherosclerosis.
Abstract:
Atherosclerosis is one of the leading causes of morbidity and mortality in the Western world. Although the clinical manifestations of this disease are well documented, the etiology and progression remain to be fully understood. Recently, the mitochondria have been implicated in important cellular processes involved in development of atherosclerosis. Despite the link between mitochondria and atherosclerosis, early-phase mechanisms of the disease have yet to be elucidated. The aim of this project was to explore the role of mitochondria in vascular smooth muscle (VSMC) dedifferentiation. A murine in vitro model, involving organ culture of aortic tissue in serum-free media, was used. Mitochondrial function was measured by high-resolution respirometry. Proteins associated with the VSMC phenotype switch, as well as mitochondrial density, were assessed by immunoblotting. The findings show that intrinsic mitochondrial Complex I activity is significantly upregulated during VSMC dedifferentiation. Diminished coupling between phosphorylation and oxidation was also found, indicating a greater ADP:ATP ratio. This data suggests increased leak in the electron transport chain and altered mitochondrial function specifically at Complex I. This project provides important information regarding the role of mitochondria in the early atherosclerotic process and that detectable changes in mitochondrial function and expression are related to VSMC dedifferentiation.
