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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Pathological pulmonary vascular remodeling is induced by type V collagen in a model of scleroderma

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Author(s):
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Marangoni, Roberta Goncalves [1, 2, 3] ; Korman, Benjamin D. [2, 3] ; Parra, Edwin R. [4] ; Velosa, Ana Paula P. [1] ; Barbeiro, V, Hermes ; Martins, Vanessa [4] ; dos Santos, Angela B. G. [4] ; Soriano, Francisco [5] ; Teodoro, Walcy R. [1] ; Silva, Pedro Leme [6] ; Tourtellotte, Warren [7] ; Capelozzi, Vera L. [4] ; Varga, John [2] ; Yoshinari, Natalino H. [1]
Total Authors: 14
Affiliation:
[1] Univ Sao Paulo, Fac Med, Rheumatol Div, Sao Paulo, SP - Brazil
[2] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 - USA
[3] Univ Rochester, Med Ctr, Div Allergy Immunol & Rheumatol, Rochester, NY 14642 - USA
[4] Univ Texas Houston, MD Anderson Canc Ctr, Dept Translat Mol Pathol, 1515 Holcombe Blvd, Houston, TX 77030 - USA
[5] Barbeiro, Hermes, V, Univ Sao Paulo, Fac Med, Clin Lab Emergency Med, Sao Paulo, SP - Brazil
[6] Univ Fed Rio de Janeiro, Carlos Chagas Fillip Biophys Inst, Lab Pulm Invest, Rio De Janeiro - Brazil
[7] Cedars Sinai Med Ctr, Dept Pathol Neurol & Neurosurg, Los Angeles, CA 90048 - USA
Total Affiliations: 7
Document type: Journal article
Source: PATHOLOGY RESEARCH AND PRACTICE; v. 220, APR 2021.
Web of Science Citations: 0
Abstract

Objective: The pulmonary vascular remodeling in systemic sclerosis (SSc) is poorly understood and animal models are lacking. Type V collagen (COLV) is elevated in SSc and is implicated in the pathogenesis, and immunization with human COLV induces SSc-like skin and lung changes in rabbits and mice. Here we tested the hypothesis that COLV immunization will induce pathological and functional changes that phenocopy SSc-associated pulmonary vascular disease. Methods: Pulmonary vascular changes in rabbits immunized with human COLV were extensively characterized by a combination of histology, electron microscopy and immunohistochemistry. Physiologic changes induced by COLV in explanted pulmonary artery rings were evaluated. The pattern of histopathologic alterations and gene expression induced in immunized rabbits were compared to those in SSc patients. Results: COLV immunization was accompanied by striking pulmonary vascular abnormalities, characterized by reduced capillary density, perivascular inflammation, endothelial cell injury and collagen accumulation, that closely phenocopy changes seen in SSc patients. Moreover, pulmonary arteries from immunized rabbits showed impaired ex vivo vascular relaxation. Expression of COL5A2 was significantly increased in the lungs from immunized rabbits (p = 0.02), as well as in patients with SSc (P = 0.02). Conclusion: COLV immunity in rabbits is associated with marked vascular remodeling in the lung that phenocopies early-stage human SSc-associated pulmonary vascular disease. COLV immunization therefore represents a novel approach to model SSc pulmonary vascular pathology. Moreover, our findings suggest that COLV might represent a novel pathogenic autoantigen in SSc and future studies with the present model should be developed for possible association with PAH. (AU)

FAPESP's process: 18/20403-6 - Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promising therapeutic targets
Grantee:Vera Luiza Capelozzi
Support Opportunities: Research Projects - Thematic Grants