Matrix Gelatinases in Atherosclerosis and Diabetic Nephropathy: Progress and Challenges.
BACKGROUND
Matrix metalloproteinases (MMPs) are zinc-dependent proteases that degrade components of the extracellular matrix (ECM). In glomerular disease, MMPs are major regulators of ECM degradation as well as structural and functional integrity in the glomerulus. In altered matrix composition diseases, glomerular damage is due to increased degradation of kidney and vessel basement membranes (BMs) by MMPs. MMP -2 and -9 are both considered as the main enzymes that degrade collagen type-IV (coll-IV), which represents the key collagenous component of ECM and constitutes the architectural structure of vessels and glomerular BM. There is growing evidence implicating MMPs in atherosclerosis as well as in cardiovascular disease (CVD) and chronic kidney disease (CKD). Specific endogenous tissue inhibitors of MMPs (TIMPs) are also implicated in CKD, CVD and diabetic nephropathy (DN).


CONCLUSIONS
The present review discusses the role of MMPs -2 and -9 in DN, as a leading cause of endstage renal disease and as a model of the link between progressive glomerulosclerosis and MMP expression.
13 Dimokratias Str. Panorama, PC 55236, Thessaloniki. Greece.
Grigorios G
GG
Dimas
First Propaedeutic Medical Department of Internal Medicine, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki. Greece.
Triantafyllos P
TP
Didangelos
First Propaedeutic Medical Department of Internal Medicine, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki. Greece.
Dimitrios M
DM
Grekas
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism
D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
Matrix metalloproteinases; atherosclerosis; diabetic nephropathy; gelatinases; glomerulosclerosis; proteinuria