A novel approach to oral apoA-I mimetic therapy.

Academic Article

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.
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    Keywords

  • Animals, Apolipoprotein A-I, Apolipoproteins E, Atherosclerosis, Cholesterol, Female, Hydroxyeicosatetraenoic Acids, Intestine, Small, Lycopersicon esculentum, Lysophospholipids, Mice, Mice, Inbred C57BL, Mice, Knockout, Peptides, Plants, Genetically Modified, Receptors, LDL, Triglycerides
  • Digital Object Identifier (doi)

    Author List

  • Chattopadhyay A; Navab M; Hough G; Gao F; Meriwether D; Grijalva V; Springstead JR; Palgnachari MN; Namiri-Kalantari R; Su F
  • Start Page

  • 995
  • End Page

  • 1010
  • Volume

  • 54
  • Issue

  • 4