Egr-1 identifies neointimal remodeling and relates to progression in human pulmonary arterial hypertension

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• 作者：Diederik E. van der Feen ; MD^a ; ^b ; ¹ ; ^{d.e.van.der.feen01@umcg.nl" class="auth_mail" title="E-mail the corresponding author} ; Michael G. Dickinson ; MD ; PhD^a ; ^b ; ¹ ; Beatrijs Bartelds ; MD ; PhD^a ; ^b ; Marinus A.J. Borgdorff ; MD ; PhD^a ; ^b ; Hannie Sietsma ; MD ; PhD^c ; ^d ; Marilyne Lé ; vy ; MD ; PhD^e ; Rolf M.F. Berger ; MD ; PhD^a ; ^b
• 关键词：pulmonary arterial hypertension ; congenital heart disease ; neointimal remodeling ; lung biopsies ; immunohistochemistry ; early growth response-1
• 刊名：Journal of Heart and Lung Transplantation
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：35
• 期：4
• 页码：481-490
• 全文大小：6810 K

文摘

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.