Abstract: An animal model for cardiovascular disease comprising one or more vascular plaque lesions formed at selected sites within a vascular segment of a nonhuman mammal. The vascular plaque lesion is formed by administering a hypercholesterolemic diet to the nonhuman mammal, inflicting an injury to the vascular wall at the selected site after a predetermined exposure to the hypercholesterolemic diet, and applying a hydrogel to the injured vascular wall. Another aspect of the invention provides a method for evaluating a test compound for an effect on atherosclerotic lesion formation comprising administering to a nonhuman mammal a hypercholesterolemic diet, and, after a defined period of time, isolating a segment of a blood vessel using a balloon catheter, inflicting an injury to the vascular wall within the isolated segment, and applying a hydrogel within the vascular segment.