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Age-related decrease in 15-lipoxygenase contributes to reduced vasorelaxation in rabbit aorta.

Xin Tang1, Nitin Aggarwal, Blythe B Holmes

  • 1Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|December 7, 2007
PubMed
Summary
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Rabbit 15-lipoxygenase-1 (15-LO-1) expression and activity decrease with age, reducing the synthesis of vasodilatory compounds. This age-related decline in 15-LO-1 impacts aortic relaxation responses to acetylcholine and arachidonic acid.

Area of Science:

  • Biochemistry
  • Physiology
  • Vascular Biology

Background:

  • Rabbit 15-lipoxygenase-1 (15-LO-1) metabolizes arachidonic acid (AA) into vasoactive epoxyeicosatrienoic acids (EETs) and trihydroxyeicosatrienoic acids (THEAs).
  • Age-dependent changes in vascular function are critical for understanding cardiovascular health.
  • The role of 15-LO-1 in age-related vascular changes requires further investigation.

Purpose of the Study:

  • To investigate the age-dependent expression of 15-LO-1 in rabbit aorta.
  • To determine the impact of aging on the synthesis of 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) and 11,12,15-trihydroxyeicosatrienoic acid (THETA).
  • To assess the correlation between 15-LO-1 activity and age-related alterations in aortic vasoactivity.

Main Methods:

  • Quantitative analysis of 15-LO-1 mRNA and protein expression in rabbit aortas across different age groups (1, 4, 8, 16 weeks).

Related Experiment Videos

  • Measurement of THETA and HEETA synthesis in aortic and mesenteric artery tissues.
  • Assessment of vasorelaxation responses to acetylcholine, arachidonic acid (AA), and sodium nitroprusside in isolated aortic rings.

    • Main Results:

    • Aortic 15-LO-1 expression (mRNA and protein) was significantly higher in 1-week-old rabbits compared to older rabbits.
    • THETA and HEETA synthesis decreased markedly with age in both aortic and mesenteric arteries.
    • Age-related decline in vasorelaxation to acetylcholine and AA was observed, while responses to sodium nitroprusside remained unchanged.

    Conclusions:

    • Aortic 15-LO-1 expression and activity are downregulated during aging in rabbits.
    • Reduced 15-LO-1 contributes to diminished synthesis of vasoactive metabolites (THETA, HEETA) in aging aortas.
    • The age-associated decrease in 15-LO-1 pathway activity correlates with impaired vascular relaxation.