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

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

Journal of Lipid Research (Apr 2013)

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

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

Affiliations

Arnab Chattopadhyay: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
Mohamad Navab: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
Greg Hough: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
Feng Gao: Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, and
David Meriwether: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
Victor Grijalva: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
James R. Springstead: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
Mayakonda N. Palgnachari: Department of Medicine, University of Alabama, Birmingham, AL 35294
Ryan Namiri-Kalantari: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
Feng Su: Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, and
Brian J. Van Lenten: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
Alan C. Wagner: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
G.M. Anantharamaiah: Department of Medicine, University of Alabama, Birmingham, AL 35294
Robin Farias-Eisner: Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, and
Srinivasa T. Reddy: To whom correspondence should be addressed [email protected]; 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 [email protected]
Alan M. Fogelman: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095

Journal volume & issue: Vol. 54, no. 4
pp. 995 – 1010

Abstract

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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.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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