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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2016 ; 311
(5
): F852-F863
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English Wikipedia
An additive effect of anti-PAI-1 antibody to ACE inhibitor on slowing the
progression of diabetic kidney disease
#MMPMID27511457
Gu C
; Zhang J
; Noble NA
; Peng XR
; Huang Y
Am J Physiol Renal Physiol
2016[Nov]; 311
(5
): F852-F863
PMID27511457
show ga
While angiotensin II blockade slows the progression of diabetic nephropathy,
current data suggest that it alone cannot stop the disease process. New therapies
or drug combinations will be required to further slow or halt disease
progression. Inhibition of plasminogen activator inhibitor type 1 (PAI-1) aimed
at enhancing ECM degradation has shown therapeutic potential in diabetic
nephropathy. Here, using a mouse model of type diabetes, the maximally
therapeutic dose of the PAI-1-neutralizing mouse monoclonal antibody (MEDI-579)
was determined and compared with the maximally effective dose of enalapril. We
then examined whether addition of MEDI-579 to enalapril would enhance the
efficacy in slowing the progression of diabetic nephropathy. Untreated
uninephrectomized diabetic db/db mice developed progressive albuminuria and
glomerulosclerosis associated with increased expression of transforming growth
factor (TGF)-?1, PAI-1, type IV collagen, and fibronectin from weeks 18 to 22,
which were reduced by MEDI-579 at 3 mg/kg body wt, similar to enalapril given
alone from weeks 12 to 22 Adding MEDI-579 to enalapril from weeks 18 to 22
resulted in further reduction in albuminuria and markers of renal fibrosis. Renal
plasmin generation was dramatically reduced by 57% in diabetic mice, a decrease
that was partially reversed by MEDI-579 or enalapril given alone but was further
restored by these two treatments given in combination. Our results suggest that
MEDI-579 is effective in slowing the progression of diabetic nephropathy in db/db
mice and that the effect is additive to ACEI. While enalapril is renal
protective, the add-on PAI-1 antibody may offer additional renoprotection in
progressive diabetic nephropathy via enhancing ECM turnover.
|Albuminuria/*drug therapy/metabolism
[MESH]
|Angiotensin-Converting Enzyme Inhibitors/*therapeutic use
[MESH]