Development of drug deliumy system for targeting to injured myocardium by a novel glycoside-binding protein

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We investigated a novel lectin that cardiomyocytes and vascular smooth muscle cells (VSMCs) express on cell surface, in order to elucidate the role of carbohydrate-modifications for regeneration and inflammation in cardiovascular diseases and to develop a drug delivery system by using a lectin. We examined the interaction of various glycoside chains with cardiomyocytes and VSMCs and cardiomyocytes by using glycoside-binding assay with various glycoside-bearing polymers-coated dishes. Cardiomyocytes and VSMCs had the interaction with N-acetylglucosamine (GIcNAc) specifically. Moreover, cardiomyocytes and VSMCs took up the GIcNAc-conjugated liposomes. From these results, we assumed that these cells have a GIcNAc-binding lectin on cell surface and tried to identify the lectin. A GIcNAc-recognizing lectin was identified as desmin and vimentin in cardiomyocytes and as vimentin in VSMCs by using two-dimensional electrophoresis and western blotting with GIcNAc-bearing polymer. To confirm whether vimentin and desmin bind to GIcNAc, we examined a binding capacity of vimentin and desmin for GIcNAc by using BIACORE. Vimentin and desmin interacted with GIcNAc-bearing polymer highly and specifically, whereas not glucose- and galactose-bearing polymers. Moreover, to examine whether these protein express on cell surface. we performed double-immunostaining of these cells with anti-vimentin or desmin antibody and fluorescence-conjugated GIcNAc-bearing polymer. We observed that these antibodies and polymer stained on the same region of cell surface by using laser scanning confocal microscopy. From these results, we suggested that as a novel function of vimentin and desmin. these proteins have a binding capacity for GIcNAc and express on surface of cardiomyocytes and vascular smooth muscle cells.