title: A novel approach to oral apoA-I mimetic therapy.
abstract: Transgenic tomato plants were constructed with an empty vector (EV) or a vector expressing an apoA-I mimetic peptide, 6F. EV or 6F tomatoes were harvested, lyophilized, ground into powder, added to Western diet (WD) at 2.2% by weight, and fed to LDL receptor-null (LDLR(-/-)) mice at 45 mg/kg/day 6F. After 13 weeks, the percent of the aorta with lesions was 4.1 ± 4%, 3.3 ± 2.4%, and 1.9 ± 1.4% for WD, WD + EV, and WD + 6F, respectively (WD + 6F vs. WD, P = 0.0134; WD + 6F vs. WD + EV, P = 0.0386; WD + EV vs. WD, not significant). While body weight did not differ, plasma serum amyloid A (SAA), total cholesterol, triglycerides, and lysophosphatidic acid (LPA) levels were less in WD + 6F mice; P < 0.0295. HDL cholesterol and paroxonase-1 activity (PON) were higher in WD + 6F mice (P = 0.0055 and P = 0.0254, respectively), but not in WD + EV mice. Plasma SAA, total cholesterol, triglycerides, LPA, and 15-hydroxyeicosatetraenoic acid (HETE) levels positively correlated with lesions (P < 0.0001); HDL cholesterol and PON were inversely correlated (P < 0.0001). After feeding WD + 6F: i) intact 6F was detected in small intestine (but not in plasma); ii) small intestine LPA was decreased compared with WD + EV (P < 0.0469); and iii) small intestine LPA 18:2 positively correlated with the percent of the aorta with lesions (P < 0.0179). These data suggest that 6F acts in the small intestine and provides a novel approach to oral apoA-I mimetic therapy.
authors: Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors: Arnab
authors: A
authors: Chattopadhyay
authors: Mohamad
authors: M
authors: Navab
authors: Greg
authors: G
authors: Hough
authors: Feng
authors: F
authors: Gao
authors: David
authors: D
authors: Meriwether
authors: Victor
authors: V
authors: Grijalva
authors: James R
authors: JR
authors: Springstead
authors: Mayakonda N
authors: MN
authors: Palgnachari
authors: Ryan
authors: R
authors: Namiri-Kalantari
authors: Feng
authors: F
authors: Su
authors: Brian J
authors: BJ
authors: Van Lenten
authors: Alan C
authors: AC
authors: Wagner
authors: G M
authors: GM
authors: Anantharamaiah
authors: Robin
authors: R
authors: Farias-Eisner
authors: Robin
authors: R
authors: Farias-Eisener
authors: Srinivasa T
authors: ST
authors: Reddy
authors: Alan M
authors: AM
authors: Fogelman
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy; D002784:Cholesterol / Q000097:blood; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D007421:Intestine, Small / Q000378:metabolism; D018551:Solanum lycopersicum / Q000235:genetics / Q000378:metabolism; D008246:Lysophospholipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D006893:Hydroxyeicosatetraenoic Acids; D008246:Lysophospholipids; D010455:Peptides; D011973:Receptors, LDL; D014280:Triglycerides; D002784:Cholesterol; C032881:lysophosphatidic acid
references: J Lipid Res. 2001 Apr;42(4):545-52
references: 11290826
references: J Lipid Res. 2011 Jun;52(6):1200-1210
references: 21444758
references: J Sci Food Agric. 2012 Apr;92(6):1297-303
references: 22095779
references: Curr Opin Lipidol. 2012 Apr;23(2):85-90
references: 22262055
references: J Lipid Res. 2009 Aug;50(8):1538-47
references: 19225094
references: Integr Biol (Camb). 2011 Apr;3(4):479-89
references: 21283904
references: Diabetes. 2010 Dec;59(12):3223-8
references: 20826564
references: Plant Cell Rep. 1996 Dec;16(3-4):235-40
references: 24177560
references: Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):9062-7
references: 15956182
references: J Lipid Res. 2008 Jun;49(6):1344-52
references: 18323573
references: Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19997-20002
references: 21041624
references: Anal Biochem. 1995 Jan 1;224(1):451-5
references: 7710111
references: J Lipid Res. 2012 Mar;53(3):437-445
references: 22167743
references: J Lipid Res. 2011 Feb;52(2):361-73
references: 21068008
references: Biochim Biophys Acta. 2012 Mar;1818(3):530-6
references: 22119776
references: J Biol Chem. 2007 Jan 19;282(3):1980-8
references: 17114186
references: Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1726-33
references: 21571685
references: Nat Rev Cardiol. 2011 May;8(5):266-77
references: 21243009
references: Circulation. 2004 Jun 29;109(25):3215-20
references: 15197147
references: Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):164-8
references: 19608977
references: Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1325-31
references: 15831812
references: J Lipid Res. 2007 Sep;48(9):1915-23
references: 17570869
references: Front Pharmacol. 2012 Mar 09;3:37
references: 22408624
references: Circulation. 2002 Jan 22;105(3):290-2
references: 11804981
references: J Lipid Res. 2008 Nov;49(11):2302-11
references: 18621920
references: Cell Metab. 2011 May 4;13(5):592-600
references: 21531341
references: Biochemistry. 1995 Jun 20;34(24):7955-65
references: 7794908
references: J Lipid Res. 2007 Nov;48(11):2344-53
references: 17693626
references: Proteins. 1993 Apr;15(4):349-59
references: 8460106
references: Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2553-60
references: 23077141
references: J Lipid Res. 2001 Jul;42(7):1096-104
references: 11441137
references: Circulation. 2003 Oct 7;108(14):1735-9
references: 14504179
references: Atherosclerosis. 2012 May;222(1):154-7
references: 22398276
references: Methods Enzymol. 1986;128:627-47
references: 3724527
references: J Inflamm Res. 2011;4:83-92
references: 22096372