NDLI: Egr-1 Expression During Neointimal Development in Flow-Associated Pulmonary Hypertension

Content Provider	PubMed Central
Author	Dickinson, Michael G. Bartelds, Beatrijs Molema, Grietje Borgdorff, Marinus A. Boersma, Bibiche Takens, Janny Michel, Weij Wichers, Pieter Sietsma, Hannie Berger, Rolf M. F.
Copyright Year	2011
Abstract	In flow-associated pulmonary arterial hypertension (PAH), increased pulmonary blood flow is an essential trigger for neointimal formation. Using microarray analysis, we recently found that the early growth response protein 1 (Egr-1) transcription factor is increased in experimental flow-associated end-stage PAH. Its role in PAH development is unknown. Here, we assessed the spatiotemporal expression of Egr-1 during neointimal development in flow-associated PAH. Flow-associated PAH was produced in rats by combining monocrotaline administration with an aortocaval shunt. Animals were sacrificed 1 day before or 1 day, 1 week, or 4 to 5 weeks after flow addition. Egr-1 expression was spatiotemporally assessed using laser microdissection, quantitative real-time PCR and immunohistochemistry. In addition, Egr-1 expression was assessed in a non-neointimal pulmonary hypertension model and in human PAH associated with congenital shunt. In 4 to 5 weeks, rats subjected to increased flow developed PAH with neointimal lesions. Egr-1 mRNA was increased 1 day after flow addition and in end-stage PAH, whereas monocrotaline only did not result in increased Egr-1 mRNA. Directly after flow addition, Egr-1 was expressed in endothelial cells. During disease development, Egr-1 protein expression increased and migrated throughout the vessel wall. In PAH patients, Egr-1 was expressed in vessels with media hypertrophy and neointimal lesions, including plexiform lesions. Thus, Egr-1 may be an important regulator in the development of pulmonary neointimal lesions induced by increased pulmonary blood flow.
Related Links	http://dx.doi.org/10.1016/j.ajpath.2011.07.030
Ending Page	2209
Page Count	11
Starting Page	2199
File Format	PDF
ISSN	00029440
e-ISSN	15252191
Journal	The American Journal of Pathology
Issue Number	5
Volume Number	179
Language	English
Publisher	American Society for Investigative Pathology
Publisher Date	2011-11-01
Access Restriction	Open
Rights Holder	American Society for Investigative Pathology
Subject Keyword	Pathology and Forensic Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

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