Biomedical subjects

Chris G Kiani

Publications and source records attributed to Chris G Kiani.

2 recordsLinked to original sources

PubMed2005

Elastin stabilizes an infarct and preserves ventricular function.

BACKGROUND: After a myocardial infarction, the injured region becomes fibrotic and the myocardial scar may expand if the ventricular wall lacks elasticity. Cardiac dilatation may precipitate the vicious cycle of progressive heart failure. The present study evaluated the functional benefits of increasing elastin within a myocardial scar using cell based gene therapy. METHODS AND RESULTS: A myocardial infarction was generated by ligation of the left anterior descending artery in rats. Six days later, 2 x 10(6) syngeneic rat endothelial cells transfected with the rat elastin gene (elastin group, n=14) or an empty plasmid (control group, n=14) were transplanted into the infarct scar. Cardiac function, left ventricular (LV) volume, and infarct size were monitored over 3 months by echocardiography, Langendorff measurements, and planimetry. Elastin deposition was evaluated in the cells and in the infarct region by Western blot assay and by histological examination. Recombinant elastin was found in the scar in the elastin group but not the control group during the 3 months after cell transplantation. Histological assessment demonstrated organized elastic fibers within the infarct region. LV volume and infarct size were significantly smaller (P<0.05) in the elastin group than in the control group. Cardiac function evaluated by echocardiography and during Langendorff perfusion was significantly better (P<0.05) in the elastin group than in the control group. CONCLUSIONS: Expressing recombinant elastin within the myocardial scar reduced scar expansion and prevented LV enlargement after a myocardial infarction. Altering matrix remodeling after an infarct preserved the LV function for at least 3 months.

Animals↗

PubMed2005

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.

Animals↗