What question did this study set out to answer?

To determine the role of the transcription factor Sox9 in extracellular matrix remodeling, stiffness, and vascular smooth muscle cell senescence during vascular aging.

February 1, 2024Circulation ResearchOpen Access

Sox9 Accelerates Vascular Aging by Regulating Extracellular Matrix Composition and Stiffness

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Authors

MFMaria FaleevaKing's College London SASadia AhmadUniversity of the Punjab KTKonstantinos TheofilatosKing's College London

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Implication

Mechanistic study demonstrates that Sox9 promotes extracellular matrix stiffening in human vascular smooth muscle cells, indicating a self-reinforcing feedback loop that accelerates vascular aging.

Key Points

To determine the role of the transcription factor Sox9 in extracellular matrix remodeling, stiffness, and vascular smooth muscle cell senescence during vascular aging.
Analyzed Sox9 and senescence marker p16 expression by immunohistochemistry in aortic tissue samples from young and aged human donors.
Modulated Sox9 levels using adenoviral overexpression and depletion in cultured young and senescent primary human vascular smooth muscle cells.
Characterized extracellular matrix mechanics, composition, and cellular phenotypes using atomic force microscopy, proteomics, and confocal microscopy.
Sox9 expression and nuclear translocation increased in senescent cells and on stiff matrices, spatially correlating with senescence marker p16 rather than calcification in human aorta.
Sox9 drove extracellular matrix stiffening and structural remodeling by altering collagen expression, reducing cellular contractility, and enhancing extracellular vesicle-mediated secretion of LH3.
Matrix produced by Sox9-depleted cells restored proliferation in senescent cells, whereas matrix from Sox9-expressing cells triggered DNA damage and senescence in proliferating cells.

Cite This Study

Faleeva et al. (2024) studied this question.

synapsesocial.com/papers/69ff1a8bb124fe58198549b4 https://doi.org/10.1161/circresaha.123.323365

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Implication

Mechanistic study demonstrates that Sox9 promotes extracellular matrix stiffening in human vascular smooth muscle cells, indicating a self-reinforcing feedback loop that accelerates vascular aging.

Sox9 Accelerates Vascular Aging by Regulating Extracellular Matrix Composition and Stiffness

Discussion

Member takes

Implication

Key Points

Cite This Study

Sox9 Accelerates Vascular Aging by Regulating Extracellular Matrix Composition and Stiffness

Discussion

Member takes

Implication

Key Points

Cite This Study

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