Aspirin, But Not Clopidogrel, Reduces Collateral Conductance in a Rabbit Model of Femoral Artery Occlusion

The objective of this study was to test the potential of aspirin and clopidogrel to influence collateral artery growth (arteriogenesis). Aspirin and clopidogrel are antiplatelet agents commonly used in the treatment of ischemic cardiovascular disease. Both inhibit platelet aggregation; however, they...

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Veröffentlicht in:Journal of the American College of Cardiology 2005-09, Vol.46 (6), p.994-1001
Hauptverfasser: Hoefer, Imo E., Grundmann, Sebastian, Schirmer, Stephan, van Royen, Niels, Meder, Benjamin, Bode, Christoph, Piek, Jan J., Buschmann, Ivo R.
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Sprache:eng
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Zusammenfassung:The objective of this study was to test the potential of aspirin and clopidogrel to influence collateral artery growth (arteriogenesis). Aspirin and clopidogrel are antiplatelet agents commonly used in the treatment of ischemic cardiovascular disease. Both inhibit platelet aggregation; however, they differ mechanistically because aspirin acts via cyclooxygenase (COX) inhibition, while clopidogrel noncompetitively antagonizes the P2Y12adenosine diphosphate receptor. We hypothesized that aspirin, due to its anti-inflammatory effects through inhibition of COX activity could inhibit arteriogenesis. Given that clopidogrel does not affect COX activity, it would be less likely to interfere with collateral artery growth. Fifty-four New Zealand White rabbits received either saline, aspirin (10 mg/kg), or clopidogrel (10 mg/kg) for seven days after femoral artery ligation. Maximal collateral conductance was assessed with fluorescent microspheres under maximal vasodilation; cellular migration and proliferation (Ki-67) was evaluated by quantitative immunohistology. Collateral conductance was significantly reduced by aspirin treatment, whereas clopidogrel had a neutral effect (saline: 0.94 ± 0.04; clopidogrel: 0.94 ± 0.05; aspirin: 0.64 ± 0.03 ml·min−1·100 mm Hg−1·g−1; p < 0.001). Ki-67 proliferation indexes were consistent with these results (saline: 23.1 ± 2.9%; clopidogrel: 23.5 ± 1.1%; aspirin: 19.2 ± 1.1% Ki-67–positive cells). Immunohistochemistry showed COX expression in collateral arteries and a significantly decreased monocyte/macrophage accumulation in the perivascular tissue after aspirin treatment. Cell adhesion molecule expression on monocytes after activation was significantly reduced by aspirin, which might explain the reduced migratory ability. In summary, clopidogrel had a neutral effect on natural arteriogenesis. Aspirin significantly inhibited collateral artery growth, probably due to its anti-inflammatory effect. Additional studies are needed to substantiate these results before translation into clinical practice.
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2005.02.094