[Effects of niacin on cell adhesion and early atherogenesis: involvement of the p38 mitogen-activated protein kinases pathway].
OBJECTIVE
To examine the effects of niacin on lysophosphatidylcholine (LPC)-induced intercellular adhesion molecule-1 (ICAM-1), and gained insight to the mechanisms.


METHODS
Human umbilical vein endothelial cell line was cultured using Medium 200 medium in incubator at 37 °C and 5% CO2 condition.Experimental groups:(1) the negative control group:medium; (2) LPC different time groups:the medium added with 20 µmol/L final concentration of LPC, were cultured for 10 min and 8 h, 24 h; (3) LPC+ p38-mitogen-activated protein kinase (p38MAPK) inhibitor (SB203580) group:the medium added with 10 µmol/L p38MAPK inhibitor (SB203580) was cultured for 1 h, then human umbilical vein endothelial cells (HUVECs) added with the LPC were cultured for 10 min, 8 h and 24 h.(4) LPC+different niacin dose group:after separately adding with 0.25, 0.5, 1 mmol/L niacin, the cells were cultured for 18 h, then HUVECs added with the LPC were cultured for 10 min, 8 h and 24 h. Cell concentration in each group was 5×10(5)/ml, inoculated in 6-well plates, each well 1 ml. Detected by Western blot analysis of pp38MAPK, ICAM-1 protein content, real-time quantitative PCR to detect endothelial cell ICAM-1 mRNA expression, cell immunofluorescence to detect LPC-induced ICAM-1 protein expression.


RESULTS
In LPC 24 h group, the expression of ICAM-1 protein was significantly increased 0.786 ± 0.02, the LPC+niacin group, ICAM-1 protein levels (0.487 ± 0.015) was significantly lower than the LPC 24 h group (P < 0.01), in LPC+SB203580 intervention group, ICAM-1 protein levels (0.461 ± 0.011) was significantly lower than that of the LPC 24 h group (P < 0.01), but did not reach the level of the control group. Adding LPC to culture for 10 min, phosphorylation of p38MAPK (pp38MAPK) reached its peak (0.47 ± 0.02), niacin could reduce the pp38MAPK (0.07 ± 0.02), SB203580 could also reduce its activity (0.11 ± 0.02). Adding LPC to culture for 8 h, ICAM-1 mRNA expression (8.16 ± 0.15) compared with the control group (1.00 ± 0.02) had a significant increase (t = 24.34, P < 0.01). Compared with the LPC 8 h, niacin reduced LPC-induced ICAM-1 mRNA expression (3.85 ± 0.14), and showed a dose-dependent manner (F = 8.06, P < 0.01), while SB203580 could not effectively reduce the ICAM-1 mRNA (8.09 ± 0.11).


CONCLUSIONS
Niacin prevented LPC-induced endothelial dysfunction by reducing expression of ICAM-1. These mechanisms appeared to be at least partly mediated by suppression of the pp38MAPK in endothelial cells. These pleiotropic effects of niacin may potentially contribute to the beneficial effects of risk reduction for atherosclerotic disease.
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Na
N
Niu
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Bo
B
Han
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Shu-zhen
SZ
Sun
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Yong-hui
YH
Yu
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Yi
Y
Wang
Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Li-jun
LJ
Wang
D050197:Atherosclerosis / Q000378:metabolism / Q000517:prevention & control; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000008:administration & dosage / Q000494:pharmacology; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D007093:Imidazoles; D008244:Lysophosphatidylcholines; D011725:Pyridines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D009525:Niacin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580