Antiproliferative effects of D-polymannuronic sulfate on rat vascular smooth muscle cells and its related mechanisms
Abstract
Aim: To investigate the inhibitory effects of D-polymannuronic sulfate (DPS) on the proliferation of rat vascular smooth muscle cells (VSMC) induced by angiotensin II (Ang II) and its related mechanisms.
Methods: The effects of DPS on Ang II-induced proliferation of VSMC were evaluated by MTT assay. The intracellular free Ca2+ concentrations, protein contents, and cell cycle were analyzed by flow cytometry.
Results: DPS 0.001 - 100 mg/L blocked the cell cycle at the G0/G1-->S transit and prevented the cells from entering into the G2/M phase, and its inhibitory effects on an increase in intracellular free Ca2+ concentrations and the protein synthesis of VSMC were also observed. Also, the suppressing actions of DPS on intracellular Ca2+ were completely blocked by L-NAME, a nitric oxide synthase inhibitor, indicating that the counteracting effects on a rise in intracellular free Ca2+ contents by DPS might be mediated by participation of NO.
Conclusion: DPS exerted an inhibitory effect on Ang II-induced proliferation of VSMC and its related mechanisms were considered to be related to its inhibition on the increment of intracellular Ca2+ concentrations, which subsequently suppressed the synthesis of DNA and protein of VSMC.
Keywords:
Methods: The effects of DPS on Ang II-induced proliferation of VSMC were evaluated by MTT assay. The intracellular free Ca2+ concentrations, protein contents, and cell cycle were analyzed by flow cytometry.
Results: DPS 0.001 - 100 mg/L blocked the cell cycle at the G0/G1-->S transit and prevented the cells from entering into the G2/M phase, and its inhibitory effects on an increase in intracellular free Ca2+ concentrations and the protein synthesis of VSMC were also observed. Also, the suppressing actions of DPS on intracellular Ca2+ were completely blocked by L-NAME, a nitric oxide synthase inhibitor, indicating that the counteracting effects on a rise in intracellular free Ca2+ contents by DPS might be mediated by participation of NO.
Conclusion: DPS exerted an inhibitory effect on Ang II-induced proliferation of VSMC and its related mechanisms were considered to be related to its inhibition on the increment of intracellular Ca2+ concentrations, which subsequently suppressed the synthesis of DNA and protein of VSMC.