1. Egr-1 identifies neointimal remodeling and relates to progression in human pulmonary arterial hypertension.
- Author
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van der Feen DE, Dickinson MG, Bartelds B, Borgdorff MA, Sietsma H, Lévy M, and Berger RM
- Subjects
- Adult, Biopsy, Disease Progression, Early Growth Response Protein 1 biosynthesis, Familial Primary Pulmonary Hypertension metabolism, Familial Primary Pulmonary Hypertension physiopathology, Female, Humans, Immunohistochemistry, Lung metabolism, Male, Middle Aged, Pulmonary Artery metabolism, DNA genetics, Early Growth Response Protein 1 genetics, Familial Primary Pulmonary Hypertension genetics, Gene Expression Regulation, Lung pathology, Pulmonary Artery pathology
- Abstract
Background: Pulmonary arterial hypertension (PAH) is hallmarked by the development of neointimal lesions. The transcription factor Egr-1 seems to play a critical role in neointimal formation in experimental PAH and was identified as a putative target for intervention. In this study we investigated whether Egr-1 is also associated with neointimal-type vascular remodeling in different forms of human PAH or pulmonary hypertension., Methods: Using immunohistochemistry, we studied Egr-1 expression specifically in a wide morphologic spectrum of pulmonary arteries in the lung tissue of 72 patients with different forms and stages of PAH, specifically idiopathic PAH (n = 18), advanced-stage congenital heart disease‒associated PAH (PAH-CHD) (n = 21), early-stage PAH-CHD (n = 19) and non-neointimal hypoxic pulmonary hypertension (PH) (n = 4), and controls (n = 10)., Results: In PAH patients, pulmonary vascular expression of Egr-1 protein was abundant, whereas it was sporadic in non-neointimal (hypoxic) PH patients and controls. In PAH-CHD, protein expression was more pronounced in patients with advanced vascular lesions compared to those with less advanced lesions, such as medial hypertrophy., Conclusions: Pulmonary vascular Egr-1 expression is significantly increased in patients with PAH, appears specifically associated with neointimal-type vascular remodeling, and correlates with disease progression. These data translate the critical role of Egr-1 in the development of experimental PAH to human pulmonary vascular disease forms., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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