Open Access

Deficiency of filamin A in smooth muscle cells protects against hypoxia‑mediated pulmonary hypertension in mice

  • Authors:
    • Yaguo Zheng
    • Hong Ma
    • Yufeng Yan
    • Peng Ye
    • Wande Yu
    • Song Lin
    • Shao-Liang Chen
  • View Affiliations

  • Published online on: January 26, 2023     https://doi.org/10.3892/ijmm.2023.5225
  • Article Number: 22
  • Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Filamin A (FLNA) is a high molecular weight cytoskeleton protein important for cell locomotion. A relationship between FLNA mutations and pulmonary arterial hypertension (PAH) has previously been reported; however, the detailed mechanism remains unclear. The present study aimed to explore the role of FLNA in vascular smooth muscle cells during the development of PAH. Smooth muscle cell (SMC)‑specific FLNA‑deficient mice were generated and the mice were then exposed to hypoxia for 28 days to build the mouse model of PAH. Human pulmonary arterial smooth muscle cells (PASMCs) were also cultured and transfected with FLNA small interfering RNA or overexpression plasmids to investigate the effects of FLNA on PASMC proliferation and migration. Notably, compared with control individuals, the expression levels of FLNA were increased in lung tissues from patients with PAH, and it was obviously expressed in the PASMCs of pulmonary arterioles. FLNA deficiency in SMCs attenuated hypoxia‑induced pulmonary hypertension and pulmonary vascular remodeling. In vitro studies suggested that absence of FLNA impaired PASMC proliferation and migration, and produced lower levels of phosphorylated (p)‑PAK‑1 and RAC1 activity. However, FLNA overexpression promoted PASMC proliferation and migration, and increased the expression levels of p‑PAK‑1 and RAC1 activity. The present study highlights the role of FLNA in pulmonary vascular remodeling; therefore, it could serve as a potential target for the treatment of PAH.
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March-2023
Volume 51 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zheng Y, Ma H, Yan Y, Ye P, Yu W, Lin S and Chen S: Deficiency of filamin A in smooth muscle cells protects against hypoxia‑mediated pulmonary hypertension in mice. Int J Mol Med 51: 22, 2023
APA
Zheng, Y., Ma, H., Yan, Y., Ye, P., Yu, W., Lin, S., & Chen, S. (2023). Deficiency of filamin A in smooth muscle cells protects against hypoxia‑mediated pulmonary hypertension in mice. International Journal of Molecular Medicine, 51, 22. https://doi.org/10.3892/ijmm.2023.5225
MLA
Zheng, Y., Ma, H., Yan, Y., Ye, P., Yu, W., Lin, S., Chen, S."Deficiency of filamin A in smooth muscle cells protects against hypoxia‑mediated pulmonary hypertension in mice". International Journal of Molecular Medicine 51.3 (2023): 22.
Chicago
Zheng, Y., Ma, H., Yan, Y., Ye, P., Yu, W., Lin, S., Chen, S."Deficiency of filamin A in smooth muscle cells protects against hypoxia‑mediated pulmonary hypertension in mice". International Journal of Molecular Medicine 51, no. 3 (2023): 22. https://doi.org/10.3892/ijmm.2023.5225