Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice

Biol Res. 2018 Sep 15;51(1):34. doi: 10.1186/s40659-018-0183-6.

Abstract

Background and aims: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice.

Methods and results: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice.

Conclusions: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Keywords: Atherosclerosis; HDL; Serum lipids; Vitamin C and E.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apolipoprotein B-48 / blood
  • Apolipoprotein B-48 / drug effects*
  • Ascorbic Acid / pharmacology*
  • Cardiotonic Agents / pharmacology
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / prevention & control
  • Cytokines / blood
  • Diet, Atherogenic
  • Dietary Supplements
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hyperlipidemias / blood
  • Hyperlipidemias / prevention & control*
  • Immunoblotting
  • Lipid Metabolism / drug effects
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / drug effects*
  • Male
  • Mice, Inbred C57BL
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / prevention & control*
  • Phospholipid Transfer Proteins / blood
  • Reference Values
  • Reproducibility of Results
  • Scavenger Receptors, Class B / blood
  • Scavenger Receptors, Class B / drug effects
  • Treatment Outcome
  • Vitamin E / pharmacology*

Substances

  • Antioxidants
  • Apolipoprotein B-48
  • Cardiotonic Agents
  • Cytokines
  • Lipoproteins, HDL
  • Phospholipid Transfer Proteins
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Vitamin E
  • Ascorbic Acid