Upregulation of the cytoskeletal-associated protein Moesin in the neointima of coronary arteries after balloon angioplasty: a new marker of smooth muscle cell migration?

Abstract

Migrating cells like coronary smooth muscle cells in restenosis change their cell shape and form cellular protrusions called filopodia. A prerequisite for filopodia formation is the rearrangement of the actin cytoskeleton. An essential role of the 78-kDa protein Moesin is described for Rho- and Rac-dependent assembly of actin filaments. In vivo Moesin is not observed in mature smooth muscle cells. The objective of this study was to demonstrate that Moesin is upregulated in migrating coronary smooth muscle cells during restenosis development. In vivo expression of Moesin was upregulated in neointimal coronary smooth muscle cells of dilated porcine coronary arteries compared to the undilated left circumflex coronary artery of the same swine. Concordant to these results Moesin expression was upregulated in migrating and invading human arterial smooth muscle cells in vitro analyzed by FACS, Western blotting and RT-PCR. In addition, the invasive potential of Moesin-positive Mel Im cells transfected with Moesin sense DNA increased by 28% as compared to mock-transfected control, whereas antisense transfected cells had a decreased invasive potential of 32%. Transfection of Moesin-negative HepG2 with Moesin sense cDNA increased the invasive potential by 43%. Finally, transfection of human arterial smooth muscle cells with Moesin sense cDNA caused an increased invasive potential of 30%. Transfection of haSMCs with antisense cDNA decreased the invasive potential by 37% in comparison to mock-transfected control. These results demonstrate for the first time an upregulation of Moesin expression in coronary smooth muscle cells of the neointima after arterial injury. The increased migrative and invasive potential of cells transfected with Moesin confirmed the functional role of Moesin in cell migration. This indicates an important role of Moesin during restenosis development.

MicroRNA-133 Controls Vascular Smooth Muscle Cell Phenotypic Switch In Vitro and Vascular Remodeling In Vivo

“…23 Adeno-miR-133 caused mRNA degradation of both Sp-1 and moesin, whereas mRNA levels of the latter 2 genes were upregulated when VSMCs were treated with anti-miR-133 ( Figure 3A and 3E). Accordingly, 2 specific luciferase reporters for Sp-1 and moesin were specifically repressed by exogenous miR-133 ( Figure 3D and 3H).…”

“…More importantly, Sp-1 mut transduction rescued the inhibitory effects on VSMC proliferation in vitro by pre-miR-133 overexpression ( Figure 3J). Finally, as moesin, as well as Sp-1, modulates VSMC migration, 1,22,23 we tested the hypothesis that miR-133 might also inhibit cell migration. On 2% FBS stimulation for 24 hours, adeno-miR-133 transfection resulted in a significant decrease of migrating VSMCs in the Boyden chamber.…”

Increase in Collagen Turnover But Not in Collagen Fiber Content Is Associated with Flow-Induced Arterial Remodeling

“…We used moesin levels as an indicator for cell migration, since increased moesin levels are associated with an increased potential of smooth muscle cells (SMC) to migrate [12, 22]. We found increased moesin levels 2 and 7 days after flow increase (p = 0.014 and p = 0.029, respectively; fig.…”

“…Blindt et al [22]described that cells transfected with moesin revealed an increased migrative and invasive potential. We used moesin levels as an indicator for cell migration, since increased moesin levels are associated with an increased potential of smooth muscle cells (SMC) to migrate [12, 22].…”

“…Moreover, we showed that moesin, a protein associated with SMC migration, was increased during outward and inward arterial remodeling and associated with increased procollagen expression. Blindt et al [22]described increased moesin expression in neointimal SMCs and increased invasive potential after moesin transfection. Although we found a significant increase in moesin expression after flow increase, there was just a tendency to increase after flow decrease.…”