Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect

Hypertension
Leonardo Y TanakaFrancisco R M Laurindo

Abstract

Whole-vessel remodeling critically determines lumen caliber in vascular (patho)physiology, and it is reportedly redox-dependent. We hypothesized that the cell-surface pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1 (peri/epicellular=pecPDI), which is known to support thrombosis, also regulates disease-associated vascular architecture. In human coronary atheromas, PDI expression inversely correlated with constrictive remodeling and plaque stability. In a rabbit iliac artery overdistension model, there was unusually high PDI upregulation (≈25-fold versus basal, 14 days postinjury), involving both intracellular and pecPDI. PecPDI neutralization with distinct anti-PDI antibodies did not enhance endoplasmic reticulum stress or apoptosis. In vivo pecPDI neutralization with PDI antibody-containing perivascular gel from days 12 to 14 post injury promoted 25% decrease in the maximally dilated arteriographic vascular caliber. There was corresponding whole-vessel circumference loss using optical coherence tomography without change in neointima, which indicates constrictive remodeling. This was accompanied by decreased hydrogen peroxide generation. Constrictive remodeling was corroborated by marked changes ...Continue Reading

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Citations

Jan 20, 2016·Hypertension·Eberhard Schulz, Thomas Münzel
Jan 16, 2019·Cell Stress & Chaperones·Thaís L S AraujoFrancisco R M Laurindo
Dec 1, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Leonardo Y TanakaFrancisco R M Laurindo
Jan 8, 2020·Antioxidants & Redox Signaling·Leonardo Y TanakaFrancisco R M Laurindo
Jul 4, 2018·Clinical Science·Percíllia V S Oliveira, Francisco R M Laurindo
Aug 25, 2020·American Journal of Physiology. Renal Physiology·Indira D PokkunuriAnees Ahmad Banday
Nov 18, 2019·Biochimica Et Biophysica Acta. General Subjects·Marcela Franco MineiroFlavia Carla Meotti
Nov 6, 2020·BMC Genomics·Daniela KajiharaFrancisco R M Laurindo
Nov 24, 2020·Free Radical Biology & Medicine·Denise C FernandesFrancisco R M Laurindo
May 5, 2021·Antioxidants & Redox Signaling·Renato Simões Gaspar, Jonathan M Gibbins

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