Regression of atherosclerosis with apple procyanidins by activating the ATP-binding cassette subfamily A member 1 in a rabbit model

Atherosclerosis. 2017 Mar:258:56-64. doi: 10.1016/j.atherosclerosis.2017.01.032. Epub 2017 Jan 27.

Abstract

Background and aims: Apple polyphenol contains abundant procyanidins, which have been associated with an anti-atherosclerosis and cholesterol-lowering effect. The aim of this study was to investigate whether apple procyanidins (APCs) feature therapeutic efficacy in terms of regressing atherosclerosis and whether this efficacy is due to mechanisms other than a cholesterol-lowering effect.

Methods: After eight weeks on an atherogenic diet, rabbits were given a normal diet for another eight weeks to normalize the increased serum lipids level. The rabbits in the baseline group were sacrificed at this stage. The control group was subsequently fed a normal diet for eight weeks, while the APCs group was administrated 50 mg/kg/day of APCs in addition to the normal diet. Serum lipids and aortic intimal-medial thickness (IMT) were serially examined, and the resected aorta was examined histologically and through molecular biology.

Results: Aortic IMT on ultrasonography and the lipid accumulation area examined using Sudan IV staining were significantly reduced in the APCs group as compared to the control group. Serum lipid profiles were not different between the groups. Immunohistochemistry showed significantly decreased staining of an oxidative stress marker and significantly increased staining of ATP-binding cassette subfamily A member 1 (ABCA1) in the APCs group. Western blotting and RT-PCR also showed increased expression of ABCA1 mRNA and its protein in the APCs group.

Conclusions: This study revealed that APCs administration causes a regression of atherosclerosis. APCs might hold promise as an anti-atherosclerotic agent.

Keywords: ATP-binding cassette; Anti-oxidant effect; Apple polyphenol; Apple procyanidins; Atherosclerotic plaque regression; Subfamily A member 1.

MeSH terms

  • ATP Binding Cassette Transporter 1 / agonists*
  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism
  • Animals
  • Aorta / drug effects*
  • Aorta / metabolism
  • Aorta / pathology
  • Aortic Diseases / metabolism
  • Aortic Diseases / pathology
  • Aortic Diseases / prevention & control*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Biflavonoids / isolation & purification
  • Biflavonoids / pharmacology*
  • Cardiovascular Agents / isolation & purification
  • Cardiovascular Agents / pharmacology*
  • Catechin / isolation & purification
  • Catechin / pharmacology*
  • Cholesterol / blood
  • Disease Models, Animal
  • Fruit / chemistry*
  • Lipoproteins, LDL / blood
  • Male
  • Malus / chemistry*
  • Oxidative Stress / drug effects
  • Phytotherapy
  • Plants, Medicinal
  • Plaque, Atherosclerotic
  • Proanthocyanidins / isolation & purification
  • Proanthocyanidins / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / blood
  • Scavenger Receptors, Class E / metabolism
  • Time Factors
  • Up-Regulation

Substances

  • ATP Binding Cassette Transporter 1
  • Biflavonoids
  • Cardiovascular Agents
  • Lipoproteins, LDL
  • Proanthocyanidins
  • RNA, Messenger
  • Reactive Oxygen Species
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein
  • procyanidin
  • Catechin
  • Cholesterol