Background: Ventricular dilation after myocardial infarction can result in heart failure. Increasing the strength and elasticity in the infarct region might prevent scar expansion and ventricular dilation. Since elastin provides strength, extensibility and resilience to tissues and maintains tissue architecture, we studied whether over expression of elastin fragments in the infarct scar could prevent scar expansion and preserve heart function. Methods and Results: A plasmid with (elastin group) or without (vector group) an elastin fragment gene was transfected into COS7 cells. In vitro study: The cells were seeded into a Gelfoam mesh and the physical characteristics of the elastin and vector meshes were measured by a mechanical stretch test (N=5/group). The elastin mesh was more elastic (p<0.05) and had more tensile strength (p<0.05) than the vector mesh. In vivo study: Six days after LAD ligation of rat hearts, 2 x 10⁶ of COS7 cells (Cell, N=7) or COS7 cells transfected with the elastin gene (Elastin, N=9) or with the plasmid vector (Vector, N=9) were transplanted into the scat tissue. Infarcted rats were used as control (Control, N=7). Over 8 weeks COS7 cell transplantation (cell group) did not affect scar size expansion and deterioration of heart function compared to the control group. In contrast, infarct expansion in the elastin group was smaller (p<0.05) than that of the vector group. Percent fractional area shortening was better maintained in the elastin group compared with the vector group (p<0.05). At 8 weeks after cell transplantation Langendorff data showed greater (p<0.01, <0.01) developed pressure and maximum dP/dt in the elastin group and a smaller left ventricular chamber volume than in the vector group. Western blot and histology illustrated accumulated elastin in the infarct scar only in the elastin group. Conclusions: Changing the extracellular matrix composition of a myocardial infarct by increasing the elastin fragment attenuated scar expansion, ventricular dilation, and onset of heart dysfunction.