Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL002058-18
Application #
8746556
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2013
Total Cost
$1,065,405
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Li, Dan; Fawaz, Maria V; Morin, Emily E et al. (2018) Effect of Synthetic High Density Lipoproteins Modification with Polyethylene Glycol on Pharmacokinetics and Pharmacodynamics. Mol Pharm 15:83-96
Liu, Yudong; Carmona-Rivera, Carmelo; Moore, Erica et al. (2018) Myeloid-Specific Deletion of Peptidylarginine Deiminase 4 Mitigates Atherosclerosis. Front Immunol 9:1680
Liu, Chao; Han, Tianxu; Stachura, David L et al. (2018) Lipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply. Nat Commun 9:1310
Yang, Zhi-Hong; Gordon, Scott M; Sviridov, Denis et al. (2017) Dietary supplementation with long-chain monounsaturated fatty acid isomers decreases atherosclerosis and alters lipoprotein proteomes in LDLr(-/-) mice. Atherosclerosis 262:31-38
Baranova, Irina N; Souza, Ana C P; Bocharov, Alexander V et al. (2017) Human SR-BII mediates SAA uptake and contributes to SAA pro-inflammatory signaling in vitro and in vivo. PLoS One 12:e0175824
Couchie, Dominique; Vaisman, Boris; Abderrazak, Amna et al. (2017) Human Plasma Thioredoxin-80 Increases With Age and in ApoE-/- Mice Induces Inflammation, Angiogenesis, and Atherosclerosis. Circulation 136:464-475
Gordon, Scott M; Remaley, Alan T (2017) High density lipoproteins are modulators of protease activity: Implications in inflammation, complement activation, and atherothrombosis. Atherosclerosis 259:104-113
Furumoto, Yasuko; Smith, Carolyne K; Blanco, Luz et al. (2017) Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction. Arthritis Rheumatol 69:148-160
Sakurai, Toshihiro; Sakurai, Akiko; Chen, Ye et al. (2017) Dietary ?-cyclodextrin reduces atherosclerosis and modifies gut flora in apolipoprotein E-deficient mice. Mol Nutr Food Res 61:
Jin, Xueting; Sviridov, Denis; Liu, Ying et al. (2016) ABCA1 (ATP-Binding Cassette Transporter A1) Mediates ApoA-I (Apolipoprotein A-I) and ApoA-I Mimetic Peptide Mobilization of Extracellular Cholesterol Microdomains Deposited by Macrophages. Arterioscler Thromb Vasc Biol 36:2283-2291

Showing the most recent 10 out of 46 publications