In the past year, we have made several new transgenic mice lines to investigate the role of LCAT in cholesterol metabolism and atherosclerosis. hapoA-I and hLCAT transgenic mice each were found to have a modest 50% increase in HDL-C. This is consistent with the known role of apoA-I as the main structural protein of HDL and with the known role of LCAT in esterifying cholesterol, which allows the maturation of HDL into a spherical choleseryl ester rich particle. When hapoA-I and hLCAT transgenic mice were crossed, over a 10-fold increase in HDL-C was observed. This suggests that under normal circumstances, LCAT may not be that rate-limiting in the maturation of HDL, but in the presence of excess apoA-I, as in the apoA-I transgenic mice, it may be rate limiting. This finding suggests that the effectiveness of acute HDL replacement therapy, which involves the intravenous infusion of apoA-I associated with phospholipids, can potentially be improved by the co-administration of recombinant LCAT. In a series of mouse infusion studies in which recombinant apoA-I, recombinant LCAT were singly or co-infused, we found that the administered HDL was more effective in the presence of infused LCAT in mobilizing excess cholesterol from peripheral tissues and in the esterification of the removed cholesterol, which promotes the hepatic excretion of cholesterol. Future studies to examine the co-infusion of apoA-I and LCAT will be tested in animal models of atherosclerosis.

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National Heart, Lung, and Blood Institute
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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:
Yang, Zhi-Hong; Bando, Masahiro; Sakurai, Toshihiro et al. (2016) Long-chain monounsaturated fatty acid-rich fish oil attenuates the development of atherosclerosis in mouse models. Mol Nutr Food Res 60:2208-2218

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