Urinary matrix metalloproteinase activities: biomarkers for plaque angiogenesis
and nephropathy in diabetes.
Authors McKittrick IB, Bogaert Y, Nadeau K, Snell-Bergeon J, Hull A, Jiang T, Wang X,
Levi M, Moulton KS
Submitted By Moshe Levi on 2/22/2012
Status Published
Journal American journal of physiology. Renal physiology
Year 2011
Date Published 12/1/2011
Volume : Pages 301 : F1326 - F1333
PubMed Reference 21921021
Abstract Diabetic complications of nephropathy and accelerated atherosclerosis are
associated with vascular remodeling and dysregulated angiogenesis. Matrix
metalloproteinases (MMP) modify extracellular matrix during vascular remodeling
and are excreted in urine of patients with vascular malformation or tumor
angiogenesis. We hypothesized that urinary MMP activities would be sensitive
biomarkers for vascular remodeling in diabetic complications. Activities of
MMP-2, MMP-9, and its complex with neutrophil gelatinase-associated lipocalin
(NGAL/MMP-9) were measured by substrate gel zymography in urine from nondiabetic
(ND) and type 1 diabetic (T1D) rodents that were susceptible to both T1D-induced
plaque angiogenesis and nephropathy, or nephropathy alone. Additionally, these
urine activities were measured in ND and T1D adolescents. Urinary MMP-9, MMP-2,
and NGAL/MMP-9 activities were increased and more prevalent in T1D compared with
ND controls. Urinary MMP-2 activity was detected in mice with T1D-induced plaque
neovascularization. In nephropathy models, urinary NGAL/MMP-9 and MMP-9
activities appeared before onset of albuminuria, whereas MMP-2 was absent or
delayed. Finally, urinary MMP activities were increased in adolescents with
early stages of T1D. Urinary MMP activities may be sensitive, noninvasive, and
clinically useful biomarkers for predicting vascular remodeling in diabetic
renal and vascular complications.

Investigators with authorship
Moshe LeviGeorgetown University