Overexpression of elastin fragments in infarcted myocardium attenuates scar expansion and heart dysfunction.
Ventricular dilation after myocardial infarction can cause heart failure. Increasing strength and elasticity in the infarct region might prevent ventricular dilation. Because elastin provides strength, extensibility, and resilience to tissues and maintains tissue architecture, we studied the effect of elastin expression in the infarct on scar expansion and heart function. COS-7 cells transfected with a plasmid with an elastin gene fragment or a vector were seeded into a Gelfoam mesh and cultured. Mechanical stretch test (n = 5/group) showed that the elastin mesh was more elastic (P < 0.05) and tensile (P < 0.05) than the vector mesh. In an in vivo study in rats, 6 days after left anterior descending coronary artery ligation, COS-7 cells (Cell group, n = 7) or COS-7 cells with elastin gene (Elastin group, n = 9) or vector (Vector group, n = 9) were transplanted into the infarct; infarcted rats served as controls (n = 7). Over 8 wk the Cell group did not demonstrate effects on scar expansion and deterioration of heart function vs. controls. In contrast, infarct expansion was smaller and heart function was better maintained in the Elastin group vs. the Vector group (P < 0.05). At 8 wk after cell transplantation Langendorff data showed that the Elastin group had greater (P < 0.01) developed pressure and a smaller left ventricular volume than the Vector group. Western blot and histology showed accumulated elastin in the Elastin group infarct. Changing the extracellular matrix composition of a myocardial infarct by increasing elastin fragment content attenuated scar expansion, ventricular dilation, and onset of heart dysfunction.
Mizuno
Tomohiro
T
Toronto General Hospital, NU 1-115, 200 Elizabeth St., Toronto, Ontario M5G 2C4, Canada.
Mickle
Donald A G
DA
Kiani
Chris G
CG
Li
Ren-Ke
RK
D000818:Animals; D001011:Aorta; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D002921:Cicatrix / Q000517:prevention & control*; D017931:DNA Primers; D004549:Elastin / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism; D005822:Genetic Vectors; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D009203:Myocardial Infarction / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D017931:DNA Primers; D010446:Peptide Fragments; D011994:Recombinant Proteins; D004549:Elastin