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P29 The transcription factor BRN-3B/(POU4F2) regulates vascular function and integrity in vivo
  1. L Mele,
  2. LJ Maskell,
  3. VS Budhram-Mahadeo
  1. Medical Molecular Biology Unit, Institute of Cardiovascular Science, University College London, UCL, Rayne Building, London, UK


Rationale Chronic hypertension is a major risk factor for stroke and coronary heart disease. Hypertension is associated with vascular smooth muscle cell (VCMCs) dysfunction, leading to vascular wall calcification and reduced vessel compliance. However, the underlying cellular mechanisms remain unclear. We previously demonstrated that loss of the transcription factor Brn-3b/(POU4F2) results in weight gain and diabetes in mice, known risk factors for hypertension. Herein we present evidences for a direct role of Brn-3b in the maintenance of vascular integrity.

Methodology Blood pressure (pressure-volume analysis or tail cuff plethysmography) was measured in wild type (WT) and Brn-3b knockout (KO) mice. Immunostaining and histological analysis were performed in the aorta of these animals. Gene expression analysis was performed using RNAseq and the expression pattern of Brn-3b was evaluated in primary VSMC cultures by immunofluorescence and qRT-PCR.

Results Brn-3b KO mice (2–6 months) developed spontaneous hypertension and vascular dysfunction such as neointimal hyperplasia, increased extracellular matrix (ECM) deposition and calcification. RNAseq analysis revealed that loss of Brn-3b in the aorta increased ECM gene expression, including collagens. Immunostaining of aortic sections from WT mice showed that Brn-3b was principally expressed in the tunica media, mostly composed of VSMC. Additionally, Brn-3b protein and mRNA were detectable in human and rodent primary VSMC cultures.

Conclusions Brn-3b loss in vivo is associated with vascular dysfunction and hypertension. Future studies will aim to investigate the role of Brn-3b in VSMC phenotypical changes.

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