{
  "abstract": "Platelet-derived growth factor (PDGF) regulates phenotypic switching within vascular smooth muscle cells, influencing proliferation and migration. Plasma membrane calcium ATPase 4 (PMCA4) is a calcium ion transporter that is highly expressed in the aorta and is known to interact with calcineurin. We therefore investigated its role in PDGF-mediated transcriptional and biological responses in aortic vascular smooth muscle cells (AoSMCWe show that the effect of 2-6 hours of PDGF stimulation in AoSMCs resulted in a significant increase in PMCA4 RNA expression. To investigate its role, we silenced PMCA4, which led to a significant reduction at the mRNA and protein levels. Transcriptomic analysis was performed using RNA sequencing (RNAseq) of the silenced primary human AoSMCs with and without PDGF stimulation. Differential gene expression analysis identified several genes, including HEG1, IL33, MELTF, MGP, PCSK9 and CBR1, which were validated using quantitative PCR (qPCR).Pathway enrichment analysis identified enrichment of inflammatory signaling pathways, including NFκB signalling. However, lentiviral luciferase reporter assays showed no significant activation of NFκB transcriptional activity. Furthermore, knockdown of PMCA4 reduced ERK1/2 phosphorylation in PDGF-stimulated cells, as demonstrated using western blotting, suggesting PMCA4 modulates MAPK signalling downstream of PDGF.These observations suggest that PMCA4 may influence AoSMC behaviour, and further studies are underway to investigate the consequences of PMCA4 loss in AoSMCs.",
  "authors": [
    {
      "affiliations": [
        "University of Wolverhampton, Wolverhampton, United Kingdom"
      ],
      "name": "Mohmad Zouabi"
    },
    {
      "affiliations": [
        "University of Wolverhampton, Wolverhampton, United Kingdom"
      ],
      "name": "Taylor Richards"
    },
    {
      "affiliations": [
        "University of Wolverhampton, Wolverhampton, United Kingdom",
        "Department of Cardiology, Heart and Lung Centre, New Cross Hospital, Wolverhampton, United Kingdom"
      ],
      "name": "Kinza Khan"
    }
  ],
  "title": "394 Regulatory function of PMCA4 in aortic smooth muscle cells and PDGF signalling",
  "uid": "8cbdeae5-44e1-5786-a4ae-4e57707639d4"
}