The effect of endothelial progenitor cells on angiotensin II-induced proliferation of cultured rat vascular smooth muscle cells.

Previous studies have demonstrated that endothelial progenitor cells (EPCs) could delay the progress of vascular remodeling in blood vessel-proliferating diseases. The proliferation of vascular smooth muscle cells (VSMCs) is a pivotal factor in cardiovascular diseases. In this study, we investigated whether EPCs could inhibit the Angiotensin II (Ang II)-induced proliferation of VSMCs. The effect of early EPC-conditioned medium (E-EPC-CM), late EPCs-CM (L-EPC-CM), and HUVEC-CM on Ang II-induced proliferation of VSMCs was assessed by BrdU incorporation, total protein content, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, and flow cytometry. Reverse transcriptase-polymerase chain reaction and Western blot were performed to analyze the effect of different CMs on Ang II-induced phosphorylations of ERK, JNK, p38, and NF-κB subunit p65 and the expressions of c-myc and c-fos. E-EPC-CM, L-EPC-CM, and HUVEC-CM significantly inhibited the Ang II-induced DNA synthesis, total protein expression, cell survival, and cell cycle progress of VSMCs. Furthermore, E-EPC-CM significantly inhibited the Ang II-induced phosphorylation of ERK, JNK, p38, and p65 (nuclear translocation of p65) and the expressions of c-myc and c-fos. Taken together, these data suggested that EPCs may delay the progress of vascular remodeling in blood vessel-proliferating diseases by inhibiting Ang II-induced proliferation of VSMCs through inactivating MAPKs and NF-κB signaling pathways and by reducing the expressions of c-myc and c-fos.