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. The method further comprises forming a vascular plaque lesion on the vascular wall at the site of the injury, delivering the test compound to the nonhuman mammal, and monitoring atherosclerotic lesion size and composition at the injured site after a defined period of exposure to the test compound.