A novel approach to oral apoA-I mimetic therapy[S]

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. A...

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Main Authors: Arnab Chattopadhyay, Mohamad Navab, Greg Hough, Feng Gao, David Meriwether, Victor Grijalva, James R. Springstead, Mayakonda N. Palgnachari, Ryan Namiri-Kalantari, Feng Su, Brian J. Van Lenten, Alan C. Wagner, G.M. Anantharamaiah, Robin Farias-Eisner, Srinivasa T. Reddy, Alan M. Fogelman
Format: Article
Language:English
Published: Elsevier 2013-04-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520422047
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author Arnab Chattopadhyay
Mohamad Navab
Greg Hough
Feng Gao
David Meriwether
Victor Grijalva
James R. Springstead
Mayakonda N. Palgnachari
Ryan Namiri-Kalantari
Feng Su
Brian J. Van Lenten
Alan C. Wagner
G.M. Anantharamaiah
Robin Farias-Eisner
Srinivasa T. Reddy
Alan M. Fogelman
spellingShingle Arnab Chattopadhyay
Mohamad Navab
Greg Hough
Feng Gao
David Meriwether
Victor Grijalva
James R. Springstead
Mayakonda N. Palgnachari
Ryan Namiri-Kalantari
Feng Su
Brian J. Van Lenten
Alan C. Wagner
G.M. Anantharamaiah
Robin Farias-Eisner
Srinivasa T. Reddy
Alan M. Fogelman
A novel approach to oral apoA-I mimetic therapy[S]
Journal of Lipid Research
6F peptide
apolipoprotein A-I mimetic peptides
atherosclerosis
lipoproteins
genetically engineered tomato plants
author_facet Arnab Chattopadhyay
Mohamad Navab
Greg Hough
Feng Gao
David Meriwether
Victor Grijalva
James R. Springstead
Mayakonda N. Palgnachari
Ryan Namiri-Kalantari
Feng Su
Brian J. Van Lenten
Alan C. Wagner
G.M. Anantharamaiah
Robin Farias-Eisner
Srinivasa T. Reddy
Alan M. Fogelman
author_sort Arnab Chattopadhyay
title A novel approach to oral apoA-I mimetic therapy[S]
title_short A novel approach to oral apoA-I mimetic therapy[S]
title_full A novel approach to oral apoA-I mimetic therapy[S]
title_fullStr A novel approach to oral apoA-I mimetic therapy[S]
title_full_unstemmed A novel approach to oral apoA-I mimetic therapy[S]
title_sort novel approach to oral apoa-i mimetic therapy[s]
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 2013-04-01
description 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.
topic 6F peptide
apolipoprotein A-I mimetic peptides
atherosclerosis
lipoproteins
genetically engineered tomato plants
url http://www.sciencedirect.com/science/article/pii/S0022227520422047
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spelling doaj-7d5e61067aba46158bf7e2d6e0f492b12021-04-28T06:06:05ZengElsevierJournal of Lipid Research0022-22752013-04-015449951010A novel approach to oral apoA-I mimetic therapy[S]Arnab Chattopadhyay0Mohamad Navab1Greg Hough2Feng Gao3David Meriwether4Victor Grijalva5James R. Springstead6Mayakonda N. Palgnachari7Ryan Namiri-Kalantari8Feng Su9Brian J. Van Lenten10Alan C. Wagner11G.M. Anantharamaiah12Robin Farias-Eisner13Srinivasa T. Reddy14Alan M. Fogelman15Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, andDepartments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095Department of Medicine, University of Alabama, Birmingham, AL 35294Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, andDepartments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095Department of Medicine, University of Alabama, Birmingham, AL 35294Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, andTo whom correspondence should be addressed sreddy@mednet.ucla.edu; Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095; Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, and; Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095; and; To whom correspondence should be addressed sreddy@mednet.ucla.eduDepartments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095Transgenic 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.http://www.sciencedirect.com/science/article/pii/S00222275204220476F peptideapolipoprotein A-I mimetic peptidesatherosclerosislipoproteinsgenetically engineered tomato plants