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Sci Rep. 2018 Feb 8;8(1):2668. doi: 10.1038/s41598-018-20763-w.

TGFβ1 reinforces arterial aging in the vascular smooth muscle cell through a long-range regulation of the cytoskeletal stiffness.

Author information

1
Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
2
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD, 21205, USA.
3
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
4
Howard Hughes Medical Institute, Baltimore, Maryland, 21218, USA.
5
Division of Nano-Bioengineering, Incheon National University, Incheon, Republic of Korea.
6
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
7
Immunobiological and Biopharmaceutical Laboratory, Department of Pharmaceutical Biochemistry Technology, University of Sao Paulo, Sao Paulo, Brazil.
8
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA. LakattaE@grc.nia.nih.gov.
9
Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. san@jhu.edu.
10
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA. san@jhu.edu.
11
Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea. san@jhu.edu.

Abstract

Here we report exquisitely distinct material properties of primary vascular smooth muscle (VSM) cells isolated from the thoracic aorta of adult (8 months) vs. aged (30 months) F344XBN rats. Individual VSM cells derived from the aged animals showed a tense internal network of the actin cytoskeleton (CSK), exhibiting increased stiffness (elastic) and frictional (loss) moduli than those derived from the adult animals over a wide frequency range of the imposed oscillatory deformation. This discrete mechanical response was long-lived in culture and persistent across a physiological range of matrix rigidity. Strikingly, the pro-fibrotic transforming growth factor β1 (TGFβ1) emerged as a specific modifier of age-associated VSM stiffening in vitro. TGFβ1 reinforced the mechanical phenotype of arterial aging in VSM cells on multiple time and length scales through clustering of mechanosensitive α5β1 and αvβ3 integrins. Taken together, these studies identify a novel nodal point for the long-range regulation of VSM stiffness and serve as a proof-of-concept that the broad-based inhibition of TGFβ1 expression, or TGFβ1 signal transduction in VSM, may be a useful therapeutic approach to mitigate the pathologic progression of central arterial wall stiffening associated with aging.

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