{
  "abstract": "Vascular smooth muscle cells (VSMCs) play a key role in atherosclerosis progression, undergoing phenotypic switching in response to mechanical stimuli such as hemodynamic pressure, stretch, and extracellular matrix stiffness.1 2 Alongside these forces, VSMCs experience interstitial flow through arterial walls, with shear stress levels ranging from 1 to over 30 dyn/cm2 depending on their proximity to fenestrations in the internal elastic lamina (IEL). This flow can increase shear stress on VSMCs near the IEL by up to 100 times compared to regions farther away.3 Under conditions of endothelial injury, VSMCs become exposed to shear stress levels similar to endothelial cells, potentially contributing to vascular remodelling and disease progression. However, the mechanisms by which VSMCs sense and respond to these fluid forces remain underexplored.Our data suggests that changes in gene expression, particularly the decrease in ABCA1 and increase in LDL-R, support a shift towards a foam cell-like phenotype in VSMCs exposed to fluid shear stress (1 or 30 dyn/cm2). Furthermore, flow stimulation triggered the formation of lipid droplets especially at higher shear stress. We identified a mechanistic role for cytosolic phospholipase A2 (cPLA2) in lipid accumulation, as inhibiting cPLA2 reduced lipid droplet formation under flow conditions. RNA sequencing data revealed distinct yet overlapping activation patterns for transcription factors, with activity depending on the presence of the glycocalyx.Multiple enzymes involved in fatty acid synthesis and elongation pathways were upregulated, including FASN, PPT2, ACSL3 and 5, and Hacd1, suggesting an increase in fatty acids that are longer or potentially more unsaturated (Fads1 & Elovl5). Concurrently, markers of beta-oxidation (CPT2, Acadl, and Hadha) were also upregulated, indicating a flow-dependent shift in VSMC phenotype.References Swiatlowska, Pamela, et al. Pressure and stiffness sensing together regulate vascular smooth muscle cell phenotype switching. Science Advances 2022;8(15):eabm3471. Wang DM, Tarbell JM. Modeling interstitial flow in an artery wall allows estimation of wall shear stress on smooth muscle cells. J Biomech Eng. 1995;117:358–363. Swiatlowska, Pamela, et al. Hypertensive pressure mechanosensing alone triggers lipid droplet accumulation and transdifferentiation of vascular smooth muscle cells to foam cells. Advanced Science 2024;11(9):2308686.",
  "authors": [
    {
      "affiliations": [
        "School of Engineering and Materials Science, Queen Mary University of London"
      ],
      "name": "Nivethitha Kota Lakshminaraasimulu"
    },
    {
      "affiliations": [
        "School of Engineering and Materials Science, Queen Mary University of London"
      ],
      "name": "Thomas Iskratsch"
    }
  ],
  "title": "P10  Interstitial Flow-Induced Phenotypic Switching of Vascular Smooth Muscle Cells: Mechanistic Insights and Vascular Implications",
  "uid": "cfd6144b-13ee-56a7-8c82-c2b1badfde45"
}