Lovastatin Inhibits Gap Junctional Communication in Cultured Aortic Smooth Muscle Cells

Background: Gap junctions, which serve as intercellular channels that allow the passage of ions and other small molecules between neighboring cells, play an important role in vital functions, including the regulation of cell growth, differentiation, and development. Statins, the 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase inhibitors, have been shown to inhibit the migration and proliferation of smooth muscle cells (SMCs) leading to an antiproliferative effect. Recent studies have shown that statins can reduce gap junction protein connexin43 (Cx43) expression both in vivo and in vitro. However, little work has been done on the effects of statins on gap junctional intercellular communication (GJIC). We hypothesized in this study that lovastatin inhibits vascular smooth muscle cells (VSMCs) migration through the inhibition of the GJIC. Methods: Rat aortic SMCs (RASMCs) were exposed to lovastatin. Vascular smooth muscle cells migration was then assessed with a Transwell migration assay. Gap junctional intercellular communication was determined by using fluorescence recovery after photobleaching (FRAP) analysis, which was performed with a laser-scanning confocal microscope. Results: The migration of the cultured RASMCs were detected by Trans. well system. Cell migration was dose-dependently inhibited with lovastatin. Compared with that in the control (110 +/- 26), the number of migrated SMCs was significantly reduced to 72 +/- 24 (P < .05), 62 +/- 18 (P < .01), and 58 +/- 19 (P < .01) at the concentration of 0.4, 2, and 10 umol/L, per field. The rate of fluorescence recovery (R) at 5 minutes after photobleaching was adopted as the functional index of GJIC. The R- value of cells exposed to lovastatin 10 umol/L for 48 hours was 24.38% +/- 4.84%, whereas the cells in the control group had an R- value of 36.11% +/- 10.53%, demonstrating that the GJIC of RASMCs was significantly inhibited by lovastatin (P < .01). Smaller concentrations of lovastatin 0.08 umol/L did not change gap junction coupling (P > .05). Conclusions: These results suggest that lovastatin inhibits migration in a dose-dependent manner by attenuating JIC. Suppression of gap junction function could add another explanation of statin-induced antiproliferative effect.