{
  "abstract": "Large extracellular vesicles (L-EVs), also known as Microvesicles (MVs), released by neutrophils, induce endothelial cell (EC) inflammation and promote atherosclerotic plaque formation by delivering biologically active molecules. However, the effect of NL-EVs on the EC proteome remains undetermined. To investigate this, neutrophils were incubated ± nLDL (native Low-density Lipoprotein 10µg/mL) to induce vesicle formation. Human coronary artery endothelial cells (HCAECs) were cultured under low oscillatory shear stress (4 dyne/cm2, oscillation frequency 1 Hz) to model blood flow at atheroprone sites. After 68 hours, NL-EVs were added for an additional 4h under flow. Data Independent Acquisition Mass Spectrometric Analysis of HCAECs cultured ± NL-EVs was performed. Quantitative and differential expression analyses revealed a distinct proteomic profile in HCAECs treated with NL-EVs compared to controls. Notably, nine core proteins (NDUFB11, NDUFB9, UQCRQ, UQCRB, COX7B, COX4I1, MT-CO2, ATP5ME, and ATP5PB) associated with the mitochondrial electron transport chain were significantly (Fold Change cut off 1.5, p < 0.05) downregulated. This suggests that NL-EVs may induce oxidative stress, leading to increased ROS production and EC dysfunction.By adopting an unbiased approach, this study has uncovered a novel role for NL-EVs in modulating mitochondrial protein levels in HCAECs. Future studies focused on assessing mitochondrial dysfunction in vitro and in vivo will determine the functional consequences of these protein changes that could provide insights into potential therapeutic strategies to prevent or reduce atherosclerosis.",
  "authors": [
    {
      "affiliations": [
        "University of Sheffield, Sheffield, United Kingdom",
        "ASTAR, Singapore, Singapore"
      ],
      "name": "Sangam Gurung"
    },
    {
      "affiliations": [
        "ASTAR, Singapore, Singapore"
      ],
      "name": "Amanda Crystal"
    },
    {
      "affiliations": [
        "ASTAR, Singapore, Singapore"
      ],
      "name": "Wu Wei"
    },
    {
      "affiliations": [
        "University of Sheffield, Sheffield, United Kingdom"
      ],
      "name": "Endre Kiss-Toth"
    },
    {
      "affiliations": [
        "University of Sheffield, Sheffield, United Kingdom"
      ],
      "name": "Victoria Ridger"
    }
  ],
  "title": "474 Proteomic profiling of human coronary artery endothelial cells exposed to neutrophil-derived large extracellular vesicles reveals changes in multiple mitochondrial-associated proteins",
  "uid": "dbea189c-0c63-5932-9701-43a7b99df8d2"
}