Simvastatin reduces CD40 expression in an experimental model of early arterialization of saphenous vein graft
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A Rabbit Venous Interposition Model Mimicking Revascularization Surgery using Vein Grafts to Assess Intimal Hyperplasia under Arterial Blood Pressure
Published on: May 15, 2020
Massimo Chello1, Cristiano Spadaccio, Amedeo Anselmi
1Department of Cardiovascular Research, Interdisciplinary Center for Biomedical Research (CIR), University Campus BioMedico of Rome, Rome, Italy. m.chello@unicampus.it
Insights
Simvastatin reduces CD40 expression in saphenous vein grafts, potentially preventing early graft failure. This study investigated the CD40-CD40L pathway in graft response to arterial pressure and Simvastatin effects.
Area of Science:
- Vascular biology and inflammation
- Cardiovascular research
- Pharmacology
Background:
- Saphenous vein graft failure is common, primarily due to thrombosis.
- The CD40-CD40L pathway links inflammation and coagulation, contributing to graft failure.
- Understanding CD40/sCD40L in vein grafts (VG) and arterial grafts (IMA) is crucial.
Purpose of the Study:
- Investigate CD40 and soluble CD40 ligand (sCD40L) in VG response to arterial pressure.
- Evaluate the effect of Simvastatin on CD40 expression in VG and IMA.
- Assess the role of the CD40-CD40L pathway in graft failure prevention.
Main Methods:
- Collected VG and IMA samples from patients without prior statin therapy.
- Subjected segments to pulsatile pressure distension and cultured with/without Simvastatin.
- Measured CD40 in tissue lysate and sCD40L in culture supernatant and serum.
Main Results:
- IMA showed lower CD40 expression than VG.
- Pressure distension increased CD40 production in VG.
- Simvastatin significantly reduced CD40 expression in both venous and arterial samples.
- Simvastatin's effect was reversed by mevalonic acid, indicating a link to the mevalonate pathway.
- Vessel walls, not just platelets, contribute to CD40 and sCD40L.
Conclusions:
- Simvastatin modulates the CD40-sCD40L pathway in both venous and arterial grafts.
- Simvastatin may be a valuable therapeutic agent for preventing graft failure.
- Targeting the CD40-CD40L pathway could reduce early graft occlusion.
Background:
Saphenous vein graft (VG) failure occurs more frequently compared with arterial grafts, and graft thrombosis represents the main cause of early occlusion. Because CD40-CD40L pathway CD40 represents a culprit link between local inflammation and coagulation cascade, we investigate the role of CD40 and its soluble ligand (sCD40L) in the immediate in vitro response of VG to arterial pressures, and the potential effects of Simvastatin (Merck Sharp&Dohme, White-house Station, NJ) supplementation.
Methods:
Samples of saphenous vein and of internal mammary artery (IMA) were obtained from sixteen patients without history of statin therapy. Segments underwent pulsatile pressure distension and culture with or without supplementation of Simvastatin. CD40 and sCD40L were assessed in tissue lysate and in culture supernatant, respectively. sCD40L serum concentrations were also measured.
Results:
During the course of the experiment, the CD40 expression was significantly lower in IMA samples compared with both distended and not distended VG. Pressure distension up-regulated the production of CD40 in VG segments after 24 and 48 h. Statin supplementation significantly reduced the expression of CD40 in both venous (P < 0.001) and arterial samples (P < 0.001). This effect of Simvastatin was not affected by the treatment with L-NAME, but it was reversed by the addition of mevalonic acid. Mean sCD40L content in culture supernatants increased over time, suggesting that not only platelets but also the vessel wall is a source of CD40 and sCD40L.
Conclusions:
Simvastatin treatment modulates endothelial CD40-sCD40L in both venous and arterial grafts, and therefore may represent a useful tool in the pharmacological prevention of graft failure.
