Gene expression profile in flow-associated pulmonary arterial hypertension with neointimal lesions

Mirjam E. van Albada, Beatrijs Bartelds*, Hans Wijnberg, Saffloer Mohaupt, Michael G. Dickinson, Regien G. Schoemaker, Krista Kooi, Frans Gerbens, Rolf M. F. Berger

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

32 Citaten (Scopus)

Samenvatting

Pulmonary arterial hypertension (PAH) is a pulmonary angioproliferative disease with high morbidity and mortality, characterized by a typical pattern of pulmonary vascular remodeling including neointimal lesions. In congenital heart disease, increased pulmonary blood flow has appeared to be a key mediator in the development of these characteristic lesions, but the molecular mechanisms underlying the pulmonary vascular lesions are largely unknown. We employed a rat model of flow-associated PAH, which induced specific pulmonary neointimal lesions. We identified gene expression profiles in rats specifically related to the addition of increased pulmonary blood flow to monocrotaline and the associated occurrence of neointimal lesions. Increased pulmonary blood flow induced the expression of the transcription factors activating transcription factor-3 (ATF3) and early growth response factor-1 (EGR-1), for which presence was confirmed in neointimal lesions. Monocrotaline alone induced increased numbers of activated mast cells and their products. We further identified molecular pathways that may be involved in treatment with the prostacyclin analog iloprost, a vasoactive compound with clinically beneficial effects in patients with PAH, which were similar to pathways described in samples from patient studies. These pathways, associated with the development of angioproliferative lesions as well as with the response to therapy in PAH, may provide new therapeutic targets.

Originele taal-2English
Pagina's (van-tot)L483-L491
Aantal pagina's9
TijdschriftAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume298
Nummer van het tijdschrift4
DOI's
StatusPublished - apr.-2010

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