PMID- 10469372
OWN - NLM
STAT- MEDLINE
DCOM- 19991021
LR  - 20211203
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 56
IP  - 3
DP  - 1999 Sep
TI  - Renin-angiotensin blockade lowers MCP-1 expression in diabetic rats.
PG  - 1037-48
AB  - BACKGROUND: Glomerular macrophage accumulation in diabetes implicates monocyte 
      recruitment mechanisms in the pathogenesis of diabetic nephropathy. To test the 
      hypothesis that overexpression of monocyte chemoattractant protein-1 (MCP-1), a 
      monocyte chemoattractant, is attenuated by renin-angiotensin system (RAS) 
      inhibition, we assessed expression of genes regulating monocyte transmigration in 
      the glomeruli of diabetic rats. METHODS: Competitive reverse 
      transcription-polymerase chain reaction (RT-PCR) was used to semiquantitate mRNA 
      expression in glomeruli harvested by sieving at serial intervals after the 
      induction of diabetes by streptozotocin in Munich-Wistar rats. Although subject 
      to limitations, competitive RT-PCR provides an objective measure suited to the 
      minute quantities of RNA extractable from glomerular isolates. RESULTS: 
      Time-dependent elevation of MCP-1 expression was dramatically suppressed by 
      treatment with the angiotensin-converting enzyme inhibitor enalapril or the AT1 
      receptor antagonist candesartan, and was closely associated with effects on 
      proteinuria and glomerular macrophage number. By contrast, no sustained 
      suppression of the cell adhesion molecules intercellular adhesion molecule-1 or 
      vascular cell adhesion molecule-1 or the classic MCP-1 stimulators tumor necrosis 
      factor-alpha or interleukin-1beta followed RAS inhibition, and suppression of 
      transforming growth factor-beta1 expression was transient. CONCLUSION: These data 
      suggest that glomerular macrophage recruitment in experimental diabetes is 
      largely determined by angiotensin-stimulated MCP-1 expression. We conclude that 
      the RAS is an important regulator of local MCP-1 expression, either directly or 
      through glomerular hemodynamic effects, and that our data strongly implicate 
      macrophage recruitment and activation in the pathogenesis of early diabetic 
      glomerular injury.
FAU - Kato, S
AU  - Kato S
AD  - Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 
      02115, USA.
FAU - Luyckx, V A
AU  - Luyckx VA
FAU - Ots, M
AU  - Ots M
FAU - Lee, K W
AU  - Lee KW
FAU - Ziai, F
AU  - Ziai F
FAU - Troy, J L
AU  - Troy JL
FAU - Brenner, B M
AU  - Brenner BM
FAU - MacKenzie, H S
AU  - MacKenzie HS
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 (Angiotensin Receptor Antagonists)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Benzimidazoles)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (DNA Primers)
RN  - 0 (Growth Substances)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (Tetrazoles)
RN  - 69PN84IO1A (Enalapril)
RN  - S8Q36MD2XX (candesartan)
SB  - IM
MH  - Angiotensin Receptor Antagonists
MH  - Angiotensin-Converting Enzyme Inhibitors/pharmacology
MH  - Animals
MH  - Base Sequence
MH  - Benzimidazoles/pharmacology
MH  - Biphenyl Compounds
MH  - Chemokine CCL2/*genetics
MH  - Cytokines/genetics
MH  - DNA Primers/genetics
MH  - Diabetes Mellitus, Experimental/*genetics/pathology/physiopathology
MH  - Diabetic Nephropathies/etiology/pathology/physiopathology
MH  - Enalapril/pharmacology
MH  - Gene Expression/drug effects
MH  - Growth Substances/genetics
MH  - Kidney Glomerulus/pathology/physiopathology
MH  - Macrophages/pathology/physiology
MH  - Male
MH  - Proteinuria/etiology
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Angiotensin, Type 1
MH  - Receptor, Angiotensin, Type 2
MH  - Renin-Angiotensin System/*drug effects/genetics/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tetrazoles/pharmacology
EDAT- 1999/09/01 00:00
MHDA- 1999/09/01 00:01
CRDT- 1999/09/01 00:00
PHST- 1999/09/01 00:00 [pubmed]
PHST- 1999/09/01 00:01 [medline]
PHST- 1999/09/01 00:00 [entrez]
AID - S0085-2538(15)46382-3 [pii]
AID - 10.1046/j.1523-1755.1999.00643.x [doi]
PST - ppublish
SO  - Kidney Int. 1999 Sep;56(3):1037-48. doi: 10.1046/j.1523-1755.1999.00643.x.