Abstract 17090: Statins Have Different Pleiotropic Effects on Human Endothelial Cells
Introduction: Statins have a variety of pleiotropic effects, like improving endothelial cell (EC) function. We hypothesized that physiochemical properties of statins may influence EC properties. Therefore, we investigated the effect of a hydrophilic (Pravastatin [Pra]) and a lipophilic (Atorvastatin [Ator]) statin on EC proliferation and migration.
Methods: Proliferation of human umbilical vein ECs was assessed by continuously measuring bioelectrical impedance (BI) for 48 h. EC migration was determined by live cell imaging for a period of 15 h at a frequency of 1 frame/15 min under low (1.5 dyne) and high (10 dyne) flow conditions. For cell proliferation and migration assays 0.1 μM and 1 μM of Ator or Pra were used. Gene expression microarray analysis was performed and transcripts with a significant flow*statin interaction were used for functional annotation clustering in DAVID. Statistical analysis was performed with mixed models.
Results: A significant main effect for statins and statin*concentration interaction on EC proliferation was observed. The significant interaction was exemplified since Ator at 0.1 μM significantly increased EC proliferation. Pra had Independent of concentration no effect. For EC migration significant main effects for flow, statin and statin concentration were found. Also a significant flow*statin°concentration*statin°type interaction was found. Under low conditions EC migration was not significantly influenced by either statin. Under high flow 1 μM Ator significantly enhanced EC migration. In contrast, Pra attenuated EC migration at both concentrations. Microarray analysis identified 619 transcripts with a significant flow*statin interaction. Pathway analysis showed that transcripts for vesicle-mediated transport, Golgi apparatus and activity of GTPases were enriched.
Conclusion: We report differential effects of statins on EC proliferation and migration. While EC proliferation and migration was increased by Ator, Pra did not influence EC proliferation and attenuated EC migration. Microarray analysis suggests that drug transport into the cell may influence EC migration. Overall, this supports the hypothesis that the physiochemical properties of statins influence their pleiotropic effects.
Author Disclosures: F. Lorenz: None. M. Bahls: None. S. Ameling: None. E. Hammer: None. A. Strohbach: None. U. Völker: None. M. Dörr: None. S.B. Felix: None. R. Busch: None.
- © 2016 by American Heart Association, Inc.