Vascular oxidant stress enhances progression and angiogenesis of experimental atheroma

Jaikirshan J Khatri ¹, Chad Johnson , Richard Magid

⁰Division of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.

Circulation +

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January 28, 2004

View abstract on PubMed

Summary

Oxidative stress in smooth muscle cells promotes arterial lesion growth and angiogenesis by increasing vascular endothelial growth factor (VEGF). This pathway may contribute to human atheroma progression and destabilization.

Area Of Science

Cardiovascular Biology
Vascular Biology
Oxidative Stress Research

Background

Oxidative stress is linked to various pathologies, but its direct role in arterial lesion progression is not fully understood.
Investigating the causative relationship between oxidative stress and arterial disease is crucial for developing effective treatments.

Purpose Of The Study

To determine the effect of smooth muscle cell (SMC)-targeted oxidative stress on arterial lesion progression.
To elucidate the molecular mechanisms linking oxidative stress to angiogenesis in arterial lesions.

Main Methods

Comparison of carotid lesion progression in wild-type and transgenic mice overexpressing p22phox in SMCs.
Measurement of hydrogen peroxide (H2O2), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor (HIF)-1alpha levels.
In vitro co-culture experiments with SMCs and endothelial cells.
Assessment of the effect of the antioxidant ebselen.

Main Results

Transgenic mice with SMC-targeted oxidative stress exhibited significantly larger arterial lesions compared to wild-type mice.
Elevated levels of H2O2, VEGF, and HIF-1alpha were observed in lesions of transgenic mice.
SMCs from transgenic mice promoted angiogenesis in vitro, and ebselen inhibited lesion progression and angiogenesis in vivo.

Conclusions

Oxidative stress in SMCs can initiate an angiogenic switch, driving experimental plaque progression and angiogenesis.
This novel pathway involving oxidative stress, VEGF, and angiogenesis may play a role in human atheroma progression and destabilization.
Targeting oxidative stress presents a potential therapeutic strategy for managing arterial lesion development.

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