Antiproliferative effects of D-polymannuronic sulfate on rat vascular smooth muscle cells and its related mechanisms.
OBJECTIVE
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.


CONCLUSIONS
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.
Zhu
H B
HB
Department of Marine Pharmacology, Marine Drugs and Food Institute, Ocean University of Qingdao, Qingdao 266003, China.
Geng
M Y
MY
Li
J
J
Guan
H S
HS
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006603:Hexuronic Acids / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats
D006603:Hexuronic Acids; C437391:polymannuronic sulfate; D000804:Angiotensin II; D004247:DNA; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester