Epidermal growth factor receptor inhibition prevents vascular calcifying extracellular vesicle biogenesis
Amirala Bakhshian Nik, Hooi Hooi Ng, Sophie K. Ashbrook, Patrick Sun, Francesco Iacoviello, Paul R. Shearing, Sérgio Bertazzo, Deniel Mero, Bohdan B. Khomtchouk, Joshua D. Hutcheson
Abstract
Here, we investigate the potential of epidermal growth factor receptor (EGFR) inhibition to prevent vascular calcification, a leading indicator of and contributor to cardiovascular morbidity and mortality. EGFR interacts and affects the trafficking of the plasma membrane scaffolding protein caveolin-1. Previous studies reported a key role for caveolin-1 in the development of specialized extracellular vesicles that mediate vascular calcification; however, no role of EGFR has been reported. We demonstrated that EGFR inhibition modulates caveolin-1 trafficking and hinders calcifying extracellular vesicle formation, which prevents vascular calcification. Given that EGFR inhibitors are clinically approved for other indications, this may represent a novel therapeutic strategy for vascular calcification.