Abstract 18896: Casein Kinase 1α Gene Therapy Facilitates Cardiac Regeneration After Myocardial Infarction in Mice
Background: Cardiomyocyte specific conditional overexpression of SDF1 prevents heart failure after permanent coronary ligation, facilitates cardiac regeneration and leads to increased casein kinase 1α (CK1α) expression.
Hypothesis: CK1α is a key element modulating cardiomyocyte regeneration after myocardial infarction.
Methods and Results: Mice underwent permanent coronary artery ligation immediately after which lentivirus was administered by intramyocardial injection in the borderzone. CK1α expression increased 76-fold 10 days after injection of lentivirus (Gateway systems, Invitrogen) expressing lenti-CK1α-GFP compared to lenti-GFP treated controls. CK1α treatment resulted in a marked increase in cardiac function demonstrated by improved left ventricular (LV) ejection fraction (CK1α-GFP [n=10]: 54±3% [mean±SEM] vs. GFP [n=10]: 43±4%, p<0.05) decreased LV mass (105±8mg vs. 138±9 mg, p<0.05) and reduced infarct size measured by trichrome staining (10±3% vs. 18±3% of LV wall, p<0.05) 4 weeks after permanent ligation. Bromodeoxyuridine (BrdU) staining revealed induced regeneration of CK+ cardiomyocytes (CM) in the borderzone of the infarct (3.8±0.8% CM nuclei, p<0.01), while BrdU+/ CK+ CM were not found in GFP virus injected mice. Cardiomyocyte cross sectional areas in the border zone and remote zone were significantly reduced in lenti-CK1α-GFP treated mice (border zone: 338±9 μm2 vs. 363±10 μm2, p<0.05, remote zone: 178±6 μm2 vs. 199±8 μm2) compared to control virus injected mice.
Conclusion: This study demonstrates for the first time that CK1α increases myocardial regeneration and improves LV function 4 weeks after myocardial infarction.
Author Disclosures: D. Obal: None. K. Katragadda: None. A. Tomlin: None. M. Book: None. A. Bhatnagar: None. Y. Guo: None. R. Bolli: None. G. Rokosh: None.
- © 2016 by American Heart Association, Inc.