We demonstrate for the first time that the eGlx can be therapeutically targeted with the novel heparanase inhibitor OVZ/HS-1638, a unique tetravalent dendrimer heparanase inhibitor with no-off target anticoagulant activity [29], to prevent microvascular dysfunction in diabetes in multiple vessel beds, i.e. eye and kidney, in a mouse model of type-2 diabetes. Here, HPSE is linked to type 2 diabetes mellitus.