Impairment of remodeling collateralization due to PAI-1. PAI-1 elevations impair fibrinolysis and contribute to a prothrombotic state in MS, PD, and T2DM. Additionally PAI-1 elevations impair Arteriogenesis. Remodeling collateralization is impaired in MS, PD, and T2DM due to elevations in PAI-1. Conversion of plasminogen to plasmin by tPA – uPA is negatively effected by elevations in PAI-1. This defect in the generation of Plasmin results in decreased conversion of latent MMPs to active MMPs and impair the remodeling necessary for the required remodeling of the preexisting arterioles to larger arterioles necessary for a more functional blood flow around obstructed epicardial coronary arteries and obstructed peripheral vascular systems in MS, PD, and T2DM.