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Modified In Vivo Matrix Gel Plug Assay for Angiogenesis Studies
Published on: June 30, 2023
Statins and angiogenesis: is it about connections?
Magomed Khaidakov1, Wenze Wang, Junaid A Khan
1Division of Cardiology, University of Arkansas for Medical Sciences and VA Medical Center, Little Rock, AR 72205, USA. mkhaidakov@uams.edu
Biochemical and Biophysical Research Communications
|July 21, 2009
Summary
Statins impact blood vessel growth differently depending on the experimental model. These cholesterol-lowering drugs promote tube formation in dispersed cells but inhibit sprouting in intact vessels by modulating VE-cadherin.
Area of Science:
- Endocrinology
- Cell Biology
- Vascular Biology
Background:
- Statins, inhibitors of HMG-CoA reductase, exhibit contradictory effects on angiogenesis.
- Previous studies have reported both pro-angiogenic and anti-angiogenic responses to statin treatment.
Purpose of the Study:
- To reconcile conflicting data on statin-induced angiogenesis.
- To investigate the differential effects of rosuvastatin and simvastatin in distinct angiogenesis models.
- To elucidate the role of endothelial cell-cell adhesion molecules in statin's vascular effects.
Main Methods:
- Utilized two in vitro and ex vivo angiogenesis models: matrigel assay with HUVECs and mouse aortic ring sprouting assay.
- Analyzed the expression of vascular endothelial cadherin (VE-cadherin) using RT-PCR and cytoimmunostaining.
- Investigated the functional impact of VE-cadherin blockade on statin-induced angiogenesis.
Main Results:
- Both rosuvastatin and simvastatin enhanced endothelial tube formation in the matrigel assay (p<0.01).
- Conversely, both statins significantly inhibited new vessel formation in the mouse aortic ring assay (p<0.01).
- Simvastatin treatment increased VE-cadherin expression in HUVECs (p<0.05), and its blockade reversed enhanced tube formation (p<0.002).
Conclusions:
- Statins modulate endothelial cell-cell adhesion via VE-cadherin, influencing angiogenesis.
- Differential effects of statins on angiogenesis depend on the cellular context (dispersed vs. intact vessels).
- VE-cadherin-mediated effects may explain statins' anti-atherosclerotic and anti-cancer properties.
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