PMID- 10760083
OWN - NLM
STAT- MEDLINE
DCOM- 20000509
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 57
IP  - 4
DP  - 2000 Apr
TI  - Very low-density lipoprotein stimulates the expression of monocyte 
      chemoattractant protein-1 in mesangial cells.
PG  - 1472-83
AB  - BACKGROUND: Elevated plasma levels of very low-density lipoprotein (VLDL) are 
      associated with an increased risk for focal glomerulosclerosis, which is 
      analogous to atherosclerosis. One feature of focal glomerulosclerosis is the 
      presence of foam cells derived from the infiltration of circulating monocytes. 
      Mesangial cells are able to express monocyte chemoattractant protein-1 (MCP-1). 
      In this study, the ability of VLDL to stimulate MCP-1 expression in mesangial 
      cells and consequent monocyte adhesion was investigated. METHODS: For adhesion 
      studies, mesangial cells isolated from Sprague-Dawley rats were treated with VLDL 
      for six hours, followed by a one-hour incubation with Tamm-Horsfall protein-1 
      (THP-1) cells. Mesangial MCP-1 mRNA levels were determined by reverse 
      transcription-polymerase chain reaction. MCP-1 protein was determined by 
      solid-phase immunoassay. RESULTS: VLDL (100 to 300 microg/mL) significantly 
      enhanced the expression and secretion of MCP-1 (54 to 285 ng/well) in mesangial 
      cells. Such an effect was accompanied by the increased adhesion of monocytes to 
      mesangial cells and later the formation of foam cells from monocytes after 
      ingesting excessive amounts of VLDL lipids. VLDL-induced MCP-1 expression and 
      monocyte adhesion were blocked by a protein kinase C inhibitor (staurosporine), 
      as well as a calcium channel blocker (diltiazem). CONCLUSIONS: Our results 
      demonstrate that elevated levels of VLDL, through the action of MCP-1, may 
      contribute to the infiltration of monocytes into the mesangium and subsequent 
      foam cell formation. Hence, VLDLs may play a role in the pathogenesis of focal 
      glomerulosclerosis. One of the mechanisms of such effect may be mediated through 
      the calcium-dependent protein kinase C pathway.
FAU - Lynn, E G
AU  - Lynn EG
AD  - Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong 
      Kong, China.
FAU - Siow, Y L
AU  - Siow YL
FAU - O, K
AU  - O K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipids)
RN  - 0 (Lipoproteins, VLDL)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/physiology
MH  - Cell Adhesion/physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Foam Cells/physiology
MH  - Glomerular Mesangium/cytology/*metabolism/physiology
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Lipids/pharmacology
MH  - Lipoproteins, VLDL/pharmacology/*physiology
MH  - Male
MH  - Monocytes/physiology
MH  - Protein Kinase C/physiology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Vascular Cell Adhesion Molecule-1/metabolism
EDAT- 2000/04/12 09:00
MHDA- 2000/05/16 09:00
CRDT- 2000/04/12 09:00
PHST- 2000/04/12 09:00 [pubmed]
PHST- 2000/05/16 09:00 [medline]
PHST- 2000/04/12 09:00 [entrez]
AID - S0085-2538(15)46897-8 [pii]
AID - 10.1046/j.1523-1755.2000.00992.x [doi]
PST - ppublish
SO  - Kidney Int. 2000 Apr;57(4):1472-83. doi: 10.1046/j.1523-1755.2000.00992.x.