P157	VEGF-induced monocyte migration is significantly improved by atorvastatin in CAD patients with hypercholesterolaemia. A novel mechanism to enhance collateral growth.
F.Czepluch, J.Waltenberger
academisch ziekenhuis Maastricht, Maastricht, NL.

Monocytes are crucially involved in the process of collateral growth/arteriogenesis. Monocyte migration towards VEGF-A is impaired in the presence of hypercholesterolemia. Statins have several pleiotropic effects partly responsible for their cardioprotective action. We have carried out a placebo-controlled, double-blinded, randomized study to test the effect of atorvastatin on monocyte function in patients with stable coronary artery disease (CAD) and hypercholesterolemia. Fifty patients with confirmed CAD and hypercholesterolemia were included into the VERACAD-STAT trial. Following informed consent and baseline assessment of VEGF-A-induced (1 ng/ml) monocyte migration using the modified Boyden chamber assay, the lipid-lowering medication was discontinued in these patients. Patients were randomized to receive either 40 mg of atorvastatin daily or placebo for a total of 4 weeks. At the end of this treatment interval, the assessment of monocyte function was repeated. Monocytes from peripheral venous blood were isolated by density gradient centrifugation followed by a negative selection for CD14 using magnetic microbeads. The migration of monocytes from patients treated with atorvastatin could be significantly stimulated with VEGF-A to 145% above baseline, while the migratory response of monocytes from the placebo group measured only 106% (p<0.0001), i.e. VEGF-A could not induce migration of their monocytes. Furthermore, LDL-C levels were significantly reduced in the atorvastatin group following treatment for 4 weeks (2.05 mmol/L), while the placebo group measured 4.07 mmol/L (p<0.001). In the present study, we demonstrate a significant improvement of monocyte function following 4-week treatment with atorvastatin 40 mg daily as compared to the placebo control. Therefore, we postulate that VEGF-A-induced and monocyte-dependent processes of collateral formation are significantly improved by atorvastatin treatment. The improvement of monocyte function is a novel therapeutic concept that can be realized by statin treatment. The improvement of monocyte function should facilitate collateral artery growth.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.