Elastin stabilizes an infarct and preserves ventricular function.

Abstract

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.

• Authors: Tomohiro Mizuno, Terrence M Yau, Richard D Weisel, Chris G Kiani, Ren-Ke Li
• Journal: Circulation (Circulation) Vol. 112 Issue 9 Suppl Pg. I81-8 (Aug 30 2005) ISSN: 1524-4539 [Electronic] United States
• PMID: 16159870 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Fusion Proteins
• Elastin

Topics

• Animals
• Cells, Cultured (metabolism, transplantation)
• Cicatrix (metabolism, pathology)
• Drug Evaluation, Preclinical
• Elastin (genetics, physiology)
• Endothelial Cells (metabolism, transplantation)
• Extracellular Matrix (ultrastructure)
• Genetic Therapy
• Heart Failure (etiology, prevention & control)
• Hypertrophy, Left Ventricular (etiology, prevention & control)
• Male
• Myocardial Infarction (complications, diagnostic imaging, pathology, physiopathology, therapy)
• Myocardium (chemistry, pathology)
• Random Allocation
• Rats
• Rats, Inbred Lew
• Recombinant Fusion Proteins (analysis, biosynthesis, physiology)
• Single-Blind Method
• Transfection
• Ultrasonography
• Ventricular Function, Left (physiology)
• Ventricular Remodeling