PMID- 16528256
OWN - NLM
STAT- MEDLINE
DCOM- 20060620
LR  - 20220227
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 69
IP  - 6
DP  - 2006 Mar
TI  - Plasminogen activator inhibitor-1 deficiency protects against aldosterone-induced 
      glomerular injury.
PG  - 1064-72
AB  - This study tests the hypothesis that plasminogen activator inhibitor-1 (PAI-1) 
      contributes to aldosterone-induced renal and cardiac injury. The effects of 
      12-week aldosterone (2.8 microg/day)/salt (1% drinking water) versus vehicle/salt 
      on renal and cardiac histology and mRNA expression were determined in wild-type 
      (WT) and PAI-1 deficient (PAI-1(-/-)) mice. Systolic blood pressure was similar 
      in aldosterone-infused WT and PAI-1(-/-) mice until 12 weeks, when it was 
      significantly higher in the WT mice. At 12 weeks, urine volume, sodium excretion, 
      and sodium/potassium ratio were similarly increased in the two 
      aldosterone-infused groups. In contrast, urine albumin excretion was greater in 
      aldosterone-infused WT mice (mean+/-s.d.: 699.0+/-873.0 microg/24 h) compared to 
      vehicle-infused WT (23.6+/-9.0 microg/24 h, P=0.003) or aldosterone-infused 
      PAI-1(-/-) mice (131.6+/-110.6 microg/24 h, P=0.007). Aldosterone increased 
      glomerular area to a greater extent in WT (4651+/-577 versus 3278+/-488 
      microm2/glomerulus in vehicle-infused WT, P<0.001) than in PAI-1(-/-) mice 
      (3713+/-705 microm2/glomerulus, P=0.001 versus aldosterone-infused WT), with 
      corresponding mesangial expansion. Renal collagen content was also increased in 
      aldosterone-infused WT versus PAI-1(-/-) mice. In WT mice, aldosterone increased 
      renal mRNA expression of PAI-1, collagen I, collagen III, osteopontin, 
      fibronectin, monocyte chemoattractant protein-1 (MCP-1), and F4/80 (all P<0.05), 
      but not transforming growth factor beta (TGF-beta). In PAI-1(-/-) mice, 
      aldosterone increased renal expression of collagen I, osteopontin, fibronectin, 
      and MCP-1, and tended to increase collagen III. Renal osteopontin expression was 
      diminished in aldosterone-treated PAI-1(-/-) compared to aldosterone-treated WT 
      mice (P=0.05). Aldosterone induced cardiac hypertrophy but not fibrosis in WT and 
      PAI-1(-/-) mice. PAI-1 contributes to aldosterone-induced glomerular injury.
FAU - Ma, J
AU  - Ma J
AD  - Division of Pediatric Nephrology, Department of Pediatrics, Vanderbilt University 
      Medical Center, Nashville, Tennessee 37232-6602, USA.
FAU - Weisberg, A
AU  - Weisberg A
FAU - Griffin, J P
AU  - Griffin JP
FAU - Vaughan, D E
AU  - Vaughan DE
FAU - Fogo, A B
AU  - Fogo AB
FAU - Brown, N J
AU  - Brown NJ
LA  - eng
GR  - DK44757/DK/NIDDK NIH HHS/United States
GR  - DK56942/DK/NIDDK NIH HHS/United States
GR  - GM07569/GM/NIGMS NIH HHS/United States
GR  - HL60906/HL/NHLBI NIH HHS/United States
GR  - HL67308/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fibronectins)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Spp1 protein, mouse)
RN  - 106441-73-0 (Osteopontin)
RN  - 4964P6T9RB (Aldosterone)
RN  - 9007-34-5 (Collagen)
RN  - 9NEZ333N27 (Sodium)
SB  - IM
MH  - Albuminuria/urine
MH  - Aldosterone/adverse effects/*pharmacology
MH  - Animals
MH  - Blood Pressure/drug effects/physiology
MH  - Chemokine CCL2/analysis/genetics
MH  - Collagen/analysis/genetics
MH  - Fibronectins/analysis/genetics
MH  - Gene Expression
MH  - Glomerulonephritis/chemically induced/physiopathology/*prevention & control/urine
MH  - Hemodynamics/physiology
MH  - Kidney Glomerulus/chemistry/*drug effects/pathology/physiopathology
MH  - Macrophages/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Myocardium/chemistry/pathology
MH  - Nephrectomy
MH  - Osteopontin
MH  - Plasminogen Activator Inhibitor 1/*deficiency/genetics/physiology
MH  - RNA, Messenger/analysis
MH  - Sialoglycoproteins/analysis/genetics
MH  - Sodium/urine
EDAT- 2006/03/11 09:00
MHDA- 2006/06/21 09:00
CRDT- 2006/03/11 09:00
PHST- 2006/03/11 09:00 [pubmed]
PHST- 2006/06/21 09:00 [medline]
PHST- 2006/03/11 09:00 [entrez]
AID - S0085-2538(15)51604-9 [pii]
AID - 10.1038/sj.ki.5000201 [doi]
PST - ppublish
SO  - Kidney Int. 2006 Mar;69(6):1064-72. doi: 10.1038/sj.ki.5000201.