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Related Experiment Videos

Hypercholesterolemia promotes endothelial dysfunction in vitamin E- and selenium-deficient rats

L Raij1, J Nagy, K Coffee

  • 1Medical Research Service, Veterans Affairs Medical Center, Minneapolis, MN 55417.

Hypertension (Dallas, Tex. : 1979)
|July 1, 1993
PubMed
Summary

High cholesterol impairs vascular function, especially when vitamin E and selenium are deficient. This deficiency increases lipid oxidation, contributing to endothelial dysfunction in atherosclerosis.

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Area of Science:

  • Cardiovascular Research
  • Nutritional Science
  • Biochemistry

Background:

  • Endothelial dysfunction, characterized by impaired endothelium-dependent relaxations, is an early feature of atherosclerosis.
  • Endothelium-derived relaxing factor (nitric oxide) dysfunction contributes to abnormal vascular tone.
  • Oxidized lipoproteins are implicated in impairing nitric oxide-mediated responses.

Purpose of the Study:

  • To investigate the in vivo effects of hypercholesterolemia on endothelial function.
  • To determine if deficiencies in vitamin E and selenium exacerbate hypercholesterolemia-induced endothelial dysfunction.

Main Methods:

  • Dahl salt-sensitive rats were fed high-cholesterol diets with varying levels of vitamin E and selenium for 18 weeks.
  • Serum cholesterol, vitamin E levels, and indicators of lipid oxidation (thiobarbituric acid-reactive substances, exhaled pentane) were measured.

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  • Systolic blood pressure and vascular histology (intimal thickening, inflammatory cell infiltration) were assessed.

    • Main Results:

    • High-cholesterol diets significantly increased serum cholesterol levels (approximately 10-fold).
    • Rats deficient in vitamin E and selenium exhibited decreased vitamin E levels and increased lipid oxidation markers.
    • Both high-cholesterol groups showed mild intimal thickening and mononuclear cell infiltration, with no significant difference in blood pressure.

    Conclusions:

    • Hypercholesterolemia induces early signs of endothelial dysfunction and vascular changes in Dahl salt-sensitive rats.
    • Deficiency in endogenous antioxidants vitamin E and selenium exacerbates lipid oxidation under hypercholesterolemic conditions.
    • These findings suggest a role for lipid oxidation in the development of endothelial dysfunction during atherosclerosis.