Evidence for a protective role of Protein Disulfide Isomerase-A1 against aortic dissection

Porto, Fernando Garcez; Tanaka, Leonardo Yuji; de Bessa, Tiphany Coralie; Oliveira, Percillia Victoria Santos; Souza, Júlia Martins Felipe de; Kajihara, Daniela; Fernandes, Carolina Gonçalves; Santos, Patricia Nolasco; Laurindo, Francisco Rafael Martins

doi:10.1016/j.atherosclerosis.2023.117283

Cited by 2 publications

(1 citation statement)

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“…45 Furthermore, the recent elegant study of Laurindo's group reported a protective effect of PDIA1 overexpression in transgenic mice (TgPDIA1) against aorta dissection in the Ang II model, without any effects of PDIA1 on blood pressure. 46 On the other hand, PDI inhibitor bacitracin decreased ERK1/2 expression in Ang II-treated rat aorta suggesting that PDIA1 could affect blood pressure via redox signaling-dependent manner. 47 In our study, we did not measure the effect of PDIA1 inhibition on blood pressure.…”

Section: Discussionmentioning

confidence: 97%

Vascular protein disulfide isomerase A1 mediates endothelial dysfunction induced by angiotensin II in mice

Kij,

Bar,

Czyzynska‐Cichon

et al. 2024

Acta Physiologica

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AimProtein disulfide isomerases (PDIs) are involved in platelet aggregation and intravascular thrombosis, but their role in regulating endothelial function is unclear. Here, we characterized the involvement of vascular PDIA1 in angiotensin II (Ang II)‐induced endothelial dysfunction in mice.MethodsEndothelial dysfunction was induced in C57BL/6JCmd male mice via Ang II subcutaneous infusion, and PDIA1 was inhibited with bepristat. Endothelial function was assessed in vivo with magnetic resonance imaging and ex vivo with a myography, while arterial stiffness was measured as pulse wave velocity. Nitric oxide (NO) bioavailability was measured in the aorta (spin‐trapping electron paramagnetic resonance) and plasma (NO2− and NO3− levels). Oxidative stress, eNOS uncoupling (DHE‐based aorta staining), and thrombin activity (thrombin–antithrombin complex; calibrated automated thrombography) were evaluated.ResultsThe inhibition of PDIA1 by bepristat in Ang II‐treated mice prevented the impairment of NO‐dependent vasodilation in the aorta as evidenced by the response to acetylcholine in vivo, increased systemic NO bioavailability and the aortic NO production, and decreased vascular stiffness. Bepristat's effect on NO‐dependent function was recapitulated ex vivo in Ang II‐induced endothelial dysfunction in isolated aorta. Furthermore, bepristat diminished the Ang II‐induced eNOS uncoupling and overproduction of ROS without affecting thrombin activity.ConclusionIn Ang II‐treated mice, the inhibition of PDIA1 normalized the NO‐ROS balance, prevented endothelial eNOS uncoupling, and, thereby, improved vascular function. These results indicate the importance of vascular PDIA1 in regulating endothelial function, but further studies are needed to elucidate the details of the mechanisms involved.

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Section: Discussionmentioning

confidence: 97%