{
  "abstract": "Smooth muscle cells (SMCs) play a fundamental role in vascular remodelling and disease pathogenesis. Platelet-derived growth factor (PDGF) is a key regulator of proliferation, migration, and phenotypic modulation. PMCA4, a plasma membrane calcium ATPase, maintains calcium homeostasis and is one of the predominantly expressed isoforms in the aorta. It has recently been shown to modulate signalling and this study investigates how PMCA4 regulates transcriptional responses to PDGF in human primary aortic smooth muscle cells (HAoSMCs).HAoSMCs were subjected to four experimental conditions: non-targeting siRNA (siNT), siNT + PDGF stimulation, PMCA4 knockdown (siPMCA4), and siPMCA4 + PDGF. RNA sequencing (RNA-seq) was performed to assess differential gene expression, followed by pathway enrichment analysis.Selected transcriptomic findings were validated using quantitative PCR (qPCR). To explore regulatory mechanisms, we utilised a lentiviral luciferase reporter assay for the NF-κB transcription factor implicated in the RNA-seq data.PDGF significantly upregulated PMCA4 expression in AoSMCs within 2–6 hours post-stimulation. Transfection with siRNA-targeting PMCA4 effectively silenced mRNA and protein expression. RNA-seq analysis of PMCA4 knockdown, with and without PDGF stimulation, revealed that silencing reduced calponin 1 (CNN1) mRNA expression by 0.49-fold (*p* = 0.0091), suggesting a shift toward a synthetic phenotype indicative of injury or disease. KEGG pathway analysis implicated several inflammatory pathways, such as NF-κB signalling. However, validation through lentiviral luciferase reporter assays showed no significant NF-κB activation.These findings suggest that PMCA4 downregulation may promote a synthetic phenotype in AoSMCs. Further validation of differentially expressed genes (DEGs) and functional assays based on bioinformatics analysis is ongoing",
  "authors": [
    {
      "affiliations": [
        "Cardiovascular Molecular Pharmacology Laboratory, School of Pharmacy, Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK"
      ],
      "name": "Mohmad G Zouabi"
    },
    {
      "affiliations": [
        "Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK"
      ],
      "name": "Taylor Richards"
    },
    {
      "affiliations": [
        "Cardiovascular Molecular Pharmacology Laboratory, School of Pharmacy, Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK"
      ],
      "name": "Nina Al-Saadi"
    },
    {
      "affiliations": [
        "Cardiovascular Molecular Pharmacology Laboratory, School of Pharmacy, Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK",
        "Department of Cardiology, Heart and Lung Centre, New Cross Hospital, Wolverhampton, UK"
      ],
      "name": "Kinza Khan"
    }
  ],
  "title": "P33  Role of PMCA4 in platelet-derived growth factor signalling in aortic smooth muscle cells",
  "uid": "3b02fd7e-7e22-5d5d-ae0e-55e6fc722758"
}