PMID- 9428473
OWN - NLM
STAT- MEDLINE
DCOM- 19980128
LR  - 20190815
IS  - 1523-6838 (Electronic)
IS  - 0272-6386 (Linking)
VI  - 31
IP  - 1
DP  - 1998 Jan
TI  - Lovastatin reduces glomerular macrophage influx and expression of monocyte 
      chemoattractant protein-1 mRNA in nephrotic rats.
PG  - 190-4
AB  - Glomerular expression of monocyte chemoattractant protein-1 (MCP-1) and 
      subsequent glomerular macrophage infiltration may play an important role in the 
      development of glomerulosclerosis. Previous studies have shown that lovastatin 
      ameliorates experimental renal disease and reduces MCP-1 expression in 
      serum-stimulated, cultured mesangial cells. We investigated the effects of 
      lovastatin on glomerular MCP-1 expression and macrophage infiltration in rats 
      with puromycin aminonucleoside (PA) nephrosis, an experimental model of renal 
      disease characterized by early macrophage infiltration. Male Sprague-Dawley rats 
      were pretreated for 5 days with either lovastatin (4 mg/kg) or vehicle. At the 
      end of pretreatment, the lovastatin-pretreated rats received a single i.v. 
      injection of PA (50 mg/kg) and continued to receive daily lovastatin thereafter. 
      The vehicle-pretreated rats received i.v. injections of either PA or saline, and 
      continued to receive daily vehicle treatment thereafter. Ten days after PA 
      injection, the vehicle-treated PA rats showed increased (P < 0.05) serum 
      cholesterol (359 +/- 25 mg/100 mL) and urine albumin excretion (343 +/- 95 mg/24 
      hr), compared with the vehicle-treated control rats (61 +/- 3 mg/100 mL and 2.5 
      +/- 0.6 mg/24 hr, respectively). Serum cholesterol (193 +/- 22 mg/dL) and urine 
      albumin excretion (255 +/- 68 mg/24 hr) were less in the lovastatin-treated PA 
      rats than in the vehicle-treated PA rats. The number of glomerular macrophages, 
      assessed as ED-1-positive cells, per glomerular profile was increased 77% in the 
      vehicle-treated PA rats (3.3 +/- 0.2) compared with the vehicle-treated control 
      rats (1.8 +/- 0.2) (P < 0.05). By contrast, the number of glomerular macrophages 
      was not elevated in the lovastatin-treated PA rats (2.3 +/- 0.2). Thus, 
      lovastatin in vivo can attenuate glomerular macrophage infiltration. This may 
      represent one mechanism by which lovastatin ameliorates experimental glomerular 
      disease.
FAU - Park, Y S
AU  - Park YS
AD  - Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55404, 
      USA.
FAU - Guijarro, C
AU  - Guijarro C
FAU - Kim, Y
AU  - Kim Y
FAU - Massy, Z A
AU  - Massy ZA
FAU - Kasiske, B L
AU  - Kasiske BL
FAU - Keane, W F
AU  - Keane WF
FAU - O'Donnell, M P
AU  - O'Donnell MP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Kidney Dis
JT  - American journal of kidney diseases : the official journal of the National Kidney 
      Foundation
JID - 8110075
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 58-60-6 (Puromycin Aminonucleoside)
RN  - 9LHU78OQFD (Lovastatin)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Kidney Glomerulus/*metabolism/pathology
MH  - Lovastatin/*pharmacology
MH  - Macrophages/*drug effects/immunology
MH  - Male
MH  - Nephrosis/chemically induced/*drug therapy
MH  - Polymerase Chain Reaction
MH  - Puromycin Aminonucleoside
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1998/01/15 00:00
MHDA- 1998/01/15 00:01
CRDT- 1998/01/15 00:00
PHST- 1998/01/15 00:00 [pubmed]
PHST- 1998/01/15 00:01 [medline]
PHST- 1998/01/15 00:00 [entrez]
AID - S0272638698000298 [pii]
AID - 10.1053/ajkd.1998.v31.pm9428473 [doi]
PST - ppublish
SO  - Am J Kidney Dis. 1998 Jan;31(1):190-4. doi: 10.1053/ajkd.1998.v31.pm9428473.