In the past year, we have made several new transgenic mice lines. We recently made the first apoC-II KO mice, using zinc finger technology. Similar to our patients with apoC-II deficiency, these mice in both the heterozygous and homozygous state had hypertriglyceridemia. We developed these mice to investigate the effect of an apoC-II mimetic peptide on triglyceride lipolysis and as a potential new therapy for patients with apoC-II deficiency. We also produced SR-BI transgenic mice and demonstrated in paper published last year in JLR that SR-BI serves as a receptor for the pro-atherogenic lipoprotein Lp(a). We also completed and published a study demonstrating that the selective endothelial expression of ABCA1, a key cholesterol efflux transporter, is anti-atherogenic. These new mouse lines will be invaluable in understanding the pathogenesis of atherosclerosis and will help guide us in developing new therapeutic strategies for the treatment of atherosclerosis.

Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2013
Total Cost
$1,065,405
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Aseem, Obaidullah; Smith, Brian T; Cooley, Marion A et al. (2014) Cubilin maintains blood levels of HDL and albumin. J Am Soc Nephrol 25:1028-36
Tabet, Fatiha; Vickers, Kasey C; Cuesta Torres, Luisa F et al. (2014) HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells. Nat Commun 5:3292
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Rousset, Xavier; Vaisman, Boris; Amar, Marcelo et al. (2009) Lecithin: cholesterol acyltransferase--from biochemistry to role in cardiovascular disease. Curr Opin Endocrinol Diabetes Obes 16:163-71

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