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Related Experiment Videos

Flow loading induces macrophage antioxidative gene expression in experimental aneurysms.

Takeshi K Nakahashi1, Katsuyuki Hoshina, Philip S Tsao

  • 1Veterans Affairs Palo Alto Health Care System, Palo Alto, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|December 17, 2002
PubMed
Summary

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Flow loading reduces abdominal aortic aneurysm (AAA) enlargement by decreasing oxidative stress. This mechanism involves increased heme oxygenase 1 (HO-1) expression, particularly in macrophages, and is similar to alpha-tocopherol therapy.

Area of Science:

  • Cardiovascular Biology
  • Vascular Surgery
  • Biomedical Engineering

Background:

  • Reactive oxygen species (ROS) are implicated as proinflammatory mediators in abdominal aortic aneurysm (AAA) disease.
  • In vitro studies show flow loading enhances antioxidative enzyme expression and limits ROS production in vascular smooth muscle cells.
  • Flow loading in rodent models limits experimental AAA enlargement and is linked to reduced clinical AAA risk.

Purpose of the Study:

  • To elucidate the mechanisms by which mechanical flow loading attenuates AAA enlargement.
  • To investigate the role of oxidative stress and specific gene expression changes in response to flow loading.

Main Methods:

  • Abdominal aortic aneurysms were created in rodents and subjected to flow loading via femoral arteriovenous fistula.

Related Experiment Videos

  • Aortic wall shear stress and relative wall strain were quantified.
  • Gene expression profiling was performed using a 384-clone DNA microarray, with key findings validated by reverse transcriptase-polymerase chain reaction and immunohistochemistry.
  • The efficacy of alpha-tocopherol was compared to flow loading.

    • Main Results:

    • Flow loading significantly reduced AAA diameter by 26% despite proximal aortic enlargement.
    • Twenty-nine genes were differentially expressed in flow-loaded AAAs, notably heme oxygenase 1 (HO-1).
    • Increased HO-1 expression was localized to macrophages within the AAA wall.
    • Alpha-tocopherol demonstrated comparable efficacy to flow loading in limiting AAA enlargement and reducing ROS production.

    Conclusions:

    • Flow loading may attenuate AAA enlargement through mechanisms involving reduced oxidative stress.
    • Wall shear stress and strain induced by flow loading appear to be key factors in this protective effect.
    • The antioxidant pathway, including HO-1 induction, plays a significant role in mitigating AAA progression.