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Exacerbated expansive vascular remodeling due to disturbed flow in male mice overexpressing protein disulfide isomerase-A1.

Exacerbated expansive vascular remodeling due to disturbed flow in male mice overexpressing protein disulfide isomerase-A1.

期刊: Physiological reports 日期: 2026-09-01 PMID: 42670219 DOI: 10.14814/phy2.71088 浏览: 9
作者: de Souza JMF, De Bessa TC, Silva AA, Fernandes CG, Tanaka LY, Laurindo FRM
JMF, d.S., TC, D.B., AA, S., CG, F., LY, T., & FRM, L. (2026). Exacerbated expansive vascular remodeling due to disturbed flow in male mice overexpressing protein disulfide isomerase-A1.. Physiological reports. https://doi.org/10.14814/phy2.71088
JMF dS, TC DB, AA S, CG F, LY T, FRM L. Exacerbated expansive vascular remodeling due to disturbed flow in male mice overexpressing protein disulfide isomerase-A1.. Physiological reports. 2026; doi: 10.14814/phy2.71088
JMF dS, TC DB, AA S, et al. Exacerbated expansive vascular remodeling due to disturbed flow in male mice overexpressing protein disulfide isomerase-A1.[J]. Physiological reports. 2026. DOI: 10.14814/phy2.71088.
@article{jmf2026,
  author = {de Souza JMF and De Bessa TC and Silva AA and Fernandes CG and Tanaka LY and Laurindo FRM},
  title = {Exacerbated expansive vascular remodeling due to disturbed flow in male mice overexpressing protein disulfide isomerase-A1.},
  journal = {Physiological reports},
  year = {2026},
  doi = {10.14814/phy2.71088},
  note = {PMID: 42670219},
}
TY  - JOUR
AU  - de Souza JMF
AU  - De Bessa TC
AU  - Silva AA
AU  - Fernandes CG
AU  - Tanaka LY
AU  - Laurindo FRM
TI  - Exacerbated expansive vascular remodeling due to disturbed flow in male mice overexpressing protein disulfide isomerase-A1.
T2  - Physiological reports
PY  - 2026
DO  - 10.14814/phy2.71088
AN  - PMID:42670219
ER  - 

摘要

Vascular expansive remodeling is involved in atherosclerosis/restenosis; however, its mechanisms need further investigation. Protein-disulfide isomerase (PDIA1), a redox chaperone from the endoplasmic reticulum and cell surface, supports vascular smooth muscle mechanoadaptation. Vascular injury repair reportedly associates with marked PDIA1 overexpression, while PDIA1 inhibition limits expansive remodeling. However, the effects of overexpressed PDIA1 in vessel remodeling are unknown. Here, we investigate the effects of transgenic constitutive PDIA1 overexpression (TgPDIA1) in carotid artery expansive remodeling in mice subjected to partial left carotid artery ligation. The ensuing disturbed flow was documented by ultrasound imaging. TgPDIA1 mice exhibited significantly larger total calibers 14 days after ligation, along with increased medial, neointimal, and total wall areas, compared with wild-type mice. These changes were exacerbated in proximal carotid, coincident with more disturbed flow. ECM analysis revealed reduced birefringent collagen in TgPDIA1 arteries, despite increased total collagen content, indicating enhanced amount but impaired collagen organization. Morphometry disclosed enhanced collagen fiber curvature and reduced elastin fiber thickness in TgPDIA1 ligated arteries. Immunohistochemistry depicted reduced α-smooth muscle actin and increased vimentin in TgPDIA1 vessels. Analogous expansive remodeling occurred in another series of mice 28 days after total carotid occlusion. These data corroborate the PDIA1 role as a mediator of expansive vascular remodeling.

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