Poster Presentations
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EGFR inhibition prevents CAV1-dependent calcifying extracellular vesicle biogenesis
Sophie Ashbrook, PhD Candidate , Florida International University
Vascular calcification represents the most significant predictor of cardiovascular events with no current therapeutic options. Osteogenically-differentiated vascular smooth muscle cells (VSMCs) release calcifying extracellular vesicles (EVs), which nucleate nascent mineral. Caveolin-1 (CAV1), a plasma membrane scaffolding protein, plays a critical role in the formation of calcifying EVs and has shown to interact with the epidermal growth factor receptor (EGFR) in cancer pathology. We hypothesized that EGFR inhibition may prevent the biogenesis of calcifying EVs by altering CAV1 trafficking. We assessed the potential of EGFR tyrosine kinase inhibition (AG1478 and PD153035, 2.5 uM, N = 3) at different time points over 28 days to prevent calcification in vitro using VSMCs cultured in osteogenic media (OS). EGFR inhibition significantly prevented the release of calcifying EVs in OS cultures when treated for 28 days (p < 0.0001), 14 days (p < 0.0001), and 7 days (p < 0.01). The amount of CAV1 released in EVs of EGFR inhibited groups also significantly decreased (p < 0.01). Our results suggest that EGFR interferes with trafficking mechanisms that are required for calcifying EV biogenesis. Given that EGFR inhibitors exhibit clinical safety, current data show that EGFR may be a propitious target in preventing vascular calcification.
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