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Endothelial alpha1-adrenoceptors regulate neo-angiogenesis
M Ciccarelli1, G Santulli, A Campanile
1Division of Internal Medicine, Department of Clinical Medicine & Cardiovascular Sciences, Federico II University of Naples, Naples, Italy.
Alpha(1)-adrenoceptors on endothelial cells negatively regulate angiogenesis. Blocking these receptors with doxazosin enhanced blood vessel formation in a rat hindlimb ischemia model, promoting tissue repair.
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Biology
- Regenerative Medicine
Background:
- Intact endothelium is crucial for post-ischaemic angiogenesis, a process regulated by endothelial receptors.
- Alpha(1)-adrenoceptors are present on endothelial cells, suggesting a potential role in regenerative processes.
Purpose of the Study:
- To investigate the expression and function of alpha(1)-adrenoceptors in endothelial cells.
- To determine the effect of alpha(1)-adrenoceptor modulation on angiogenesis in a preclinical model.
Main Methods:
- Evaluated alpha(1)-adrenoceptor subtypes in rat endothelial cells in vitro.
- Assessed in vivo angiogenesis in a rat hindlimb ischemia model using laser Doppler, angiography, and histology.
- Administered alpha(1)-adrenoceptor agonist (phenylephrine) or antagonist (doxazosin).
Main Results:
- In vitro, doxazosin enhanced endothelial cell proliferation, migration, and tubule formation, while phenylephrine inhibited these processes.
- In vivo, increased alpha(1)-adrenoceptor density was observed in ischaemic hindlimbs.
- Doxazosin treatment improved angiogenesis in the ischaemic hindlimb without affecting systemic blood pressure.
Conclusions:
- Endothelial alpha(1)-adrenoceptors negatively regulate angiogenesis.
- Targeting alpha(1)-adrenoceptors may represent a therapeutic strategy to promote vascular regeneration.
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