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Selected Publication:
Biasin, V.
Hypoxia-induced vascular remodelling: identification of new molecular target
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] ; 2014. pp. 112
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- Authors Med Uni Graz:
- Biasin Valentina
- Advisor:
- Olschewski Andrea
- Altmetrics:
- Abstract:
- A hallmark of pulmonary hypertension (PH) is vascular remodeling characterized by enhanced human pulmonary artery smooth muscle cell (hPASMCs) proliferation. In this study we hypothesized that transcription factors play a crucial role in the remodeling process. Therefore, we aimed to identify the regulation and the role of the AP-1 transcription factors in the development of vascular remodeling. Here, we showed that AP-1 has a crucial role in proliferation of hPASMCs induced by ET-1 and PDGF-BB, well known growth factors involved in PH development. Moreover, overexpression in mice of an AP-1 member, fra-2, induced increased RVSP (right ventricular systolic pressure) together with thickening of the vessel wall in the lung. Further analysis revealed AP-1 dependent regulation of a novel protease, meprin ß, which contributed to proliferation of hPASMCs. Expression of AP-1 and meprin ß was confirmed in animal model and importantly in human samples. These findings shed light on the molecular mechanism underlying the remodeling process. Moreover, our study emphasizes the importance of AP-1 transcription family, as a central regulator of proliferation and as well as a direct regulator of downstream target genes, which might be involved in the vascular remodeling process.