Abstract
Hyperhomocysteinemia (HHcy), a syndrome displayed by high concentration of homocysteine (Hcy) in blood has been demonstrated as a significant risk factor for cardiovascular disease (CVD). We have shown that Hcy leaded to endothelial cells (EC) injuries through inhibition of proliferation and migration. Previously we have demonstrated a Hcy specifically induced gene, Carom from cultured EC and shown its inhibition of EC migration by wound healing assay. Here, through further biochemical studies, we explore mechanistic insights behind these regulations. Carom protein belongs to Bin‐Amphiphysin‐Rvs (BAR) superfamily and specifically it is a FBAR protein since it displays Fes/CIP homology (FCH) domain on N‐terminus. Using biotin homologue to label plasma membrane proteins, we find Carom overexpression with adenovirus transduction increases Vascular endothelial growth factor receptor 2 (VEGFR2) internalization in human vein umbilical endothelial cells (HUVEC) after VEGFA stimulation. The same phenomena also exist in Hcy pretreated ECs. This process is mainly dependent on clathrin mediated endocytosis, since both Monensin and dynamin GTPase inhibitor MitMAB eliminate Carom's effects on VEGFR2 endocytosis. The VEGFR2 trafficking is tightly correlated with VEGFR2 protein levels. Carom adenovirus transduction leads to significant reduction of total cellular VEGFR2 levels. Mass spectrometric analysis of Carom interacting proteins in ECs show some partner proteins are involved in subcellular organelle trafficking and cytoskeleton organization, suggesting co‐ordinations between Carom and these partners in regulating receptor endocytosis, sorting and its function. Regulation of VEGFR2 trafficking and the ensuing signaling pathways are one of the major causes accounted for Carom's inhibitory effects on EC migration.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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