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...
Main Authors: | , , , , , , , , , , , , , , , |
---|---|
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 |
id |
doaj-7d5e61067aba46158bf7e2d6e0f492b1 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
work_keys_str_mv |
AT arnabchattopadhyay anovelapproachtooralapoaimimetictherapys AT mohamadnavab anovelapproachtooralapoaimimetictherapys AT greghough anovelapproachtooralapoaimimetictherapys AT fenggao anovelapproachtooralapoaimimetictherapys AT davidmeriwether anovelapproachtooralapoaimimetictherapys AT victorgrijalva anovelapproachtooralapoaimimetictherapys AT jamesrspringstead anovelapproachtooralapoaimimetictherapys AT mayakondanpalgnachari anovelapproachtooralapoaimimetictherapys AT ryannamirikalantari anovelapproachtooralapoaimimetictherapys AT fengsu anovelapproachtooralapoaimimetictherapys AT brianjvanlenten anovelapproachtooralapoaimimetictherapys AT alancwagner anovelapproachtooralapoaimimetictherapys AT gmanantharamaiah anovelapproachtooralapoaimimetictherapys AT robinfariaseisner anovelapproachtooralapoaimimetictherapys AT srinivasatreddy anovelapproachtooralapoaimimetictherapys AT alanmfogelman anovelapproachtooralapoaimimetictherapys AT arnabchattopadhyay novelapproachtooralapoaimimetictherapys AT mohamadnavab novelapproachtooralapoaimimetictherapys AT greghough novelapproachtooralapoaimimetictherapys AT fenggao novelapproachtooralapoaimimetictherapys AT davidmeriwether novelapproachtooralapoaimimetictherapys AT victorgrijalva novelapproachtooralapoaimimetictherapys AT jamesrspringstead novelapproachtooralapoaimimetictherapys AT mayakondanpalgnachari novelapproachtooralapoaimimetictherapys AT ryannamirikalantari novelapproachtooralapoaimimetictherapys AT fengsu novelapproachtooralapoaimimetictherapys AT brianjvanlenten novelapproachtooralapoaimimetictherapys AT alancwagner novelapproachtooralapoaimimetictherapys AT gmanantharamaiah novelapproachtooralapoaimimetictherapys AT robinfariaseisner novelapproachtooralapoaimimetictherapys AT srinivasatreddy novelapproachtooralapoaimimetictherapys AT alanmfogelman novelapproachtooralapoaimimetictherapys |
_version_ |
1721504135447052288 |
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 |