Serum metalloproteinases MMP-2, MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in patients on hemodialysis

“…These MMPs and TIMPs include MMP-2 and -9 and TIMP-1 and -4. Diabetes affects ECM degradation, and activities of MMPs and TIMPs mostly regulate this process (27). Type IV collagenases, MMP-2 and -9, have been studied extensively in various glomerular diseases with conflicting results (10,14,26,27).…”

Section: Glomerular Tissue Levels Of Hcy and Nitric Oxide (No)mentioning

confidence: 99%

Ciglitazone, a PPARγ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance

Sen¹,

Rodríguez²,

Tyagi³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Sen U, Rodriguez WE, Tyagi N, Kumar M, Kundu S, Tyagi SC. Ciglitazone, a PPAR␥ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance. Am J Physiol Endocrinol Metab 295: E1205-E1212, 2008. First published September 9, 2008 doi:10.1152/ajpendo.90534.2008.-Diabetes and hyperhomocysteinemia (HHcy) are two independent risk factors for glomeruloslerosis and renal insufficiency. Although PPAR␥ agonists such as ciglitazone (CZ) are known to modulate diabetic nephropathy, the role of CZ in diabetes-associated HHcy and renopathy is incompletely defined. We tested the hypothesis that induction of PPAR␥ by CZ decreases tissue Hcy level; this provides a protective role against diabetic nephropathy. C57BL/6J mice were administered alloxan to create diabetes. Mice were grouped to 0, 1, 10, 12, and 16 wk of treatment; only 12-and 16-wk animals received CZ in drinking water after a 10-wk alloxan treatment. In diabetes, PPAR␥ cDNA, mRNA, and protein expression were repressed, whereas an increase in plasma and glomerular Hcy levels was observed. CZ normalized PPAR␥ mRNA and protein expression and glomerular level of Hcy, whereas plasma level of Hcy remained unchanged. GFR was dramatically increased at 1-wk diabetic induction, followed by hypofiltration at 10 wk, and was normalized by CZ treatment. This result corroborated with glomerular and preglomerular arteriole histology. A steady-state increase of RVR in diabetic mice became normal with CZ treatment. CZ ameliorated decrease bioavailability of NO in the diabetic animal. Glomerular MMP-2 and MMP-9 activities as well as TIMP-1 expression were increased robustly in diabetic mice and normalized with CZ treatment. Interestingly, TIMP-4 expression was opposite to that of TIMP-1 in diabetic and CZ-treated groups. These results suggested that diabetic nephropathy exacerbated glomerular tissue level of Hcy, and this caused further deterioration of glomerulus. CZ, however, protected diabetic nephropathy in part by activating PPAR␥ and clearing glomerular tissue Hcy.peroxisome proliferator-activated receptor-␥; matrix metalloproteinase; tissue inhibitor of metalloproteinases; glomerulosclerosis PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-␥ (PPAR␥) is a member of nuclear hormone receptor superfamily of ligandactivated transcription factors. It plays important roles in maintaining glucose and lipid homeostasis (39). The PPAR␥ agonists, such as ciglitazone (CZ), are agents that improve glycemic control by increasing insulin sensitivity (5). These agonists also mediate direct antiatherogenic effects in the diabetic vasculature that are independent of their metabolic actions (4). In the pathogenesis of diabetic vasculopathies, such as in glomerulosclerosis, downregulated PPAR␥ expression is associated with matrix accumulation and glomerulonephritis (23,30,39). Several studies have shown the efficacy of PPAR␥ agonists to ameliorate the progression of glomerulosclerosis (15) and have suggested that PPAR␥ ligands have a direct beneficial renal effect. However, the role...

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“…In the case of three vessel CAD, it was 1.53, 2.33 and 3.55, respectively. However, no studies are available as a direct reference to these data and to best to our knowledge, this study is the first attempt to assess the effect of CRF on the extent of CAD in coronarography patients [16][17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Coronary artery atherosclerosis in patients with the initial and the early stage of chronic renal failure

2009

Self Cite

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AbstractThe recent clinical data indicate that the initial and the early stages of chronic renal failure (CRF) may lead to increased incidence of cardiovascular complications and increased extent of coronary artery disease (CAD). This retrospective study was aimed to determine the effects of coexisting diabetes mellitus type 2 (DM-2) and the extent of atherosclerosis in coronary vessels in patients with mildly reduced kidney function (glomerular filtration rate GFR = 89–60 ml/min) and moderately reduced kidney function (GFR = 59–30 ml/min). The study patients included 53 subjects with creatinine concentration above 120 μmol/l as a cut-off level for the initial stage and compensated CRF. The distributions of coronary artery stenosis were also analysed with respect to DM-2 coexistence and levels of haemoglobin glikolised (HbA1c). The odds ratio of pathological changes in coronary arteries in patients with GFR = 44–30 ml/min, with respect to the number of affected vessels — only one, more than one or more than two — were 7.22, 4.90 and 3.55, respectively. In CRF patients with GFR = 60–89 ml/min the odds ratio of one, more than one and more than two vessels with stenosis and CAD was 1.93, 1.70 and 1.53, respectively. DM-2 was not related to the risk of significant coronary artery stenosis and did not enhance the pre-existing changes in the study setting. Our results demonstrate that the initial and the early stages of CRF were significant risk factors for coronary stenoses and for enhancing the pre-existing changes.

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Serum metalloproteinases MMP-2, MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in patients on hemodialysis

Abstract: The MMP-9/TIMP-1 ratio increased during HD sessions, although their absolute levels were lowered. This change may represent a chronic state of enhanced fibrosis in patients undergoing HD.

Cited by 80 publications

References 18 publications

Matrix metalloproteinases in kidney homeostasis and diseases

Matrix metalloproteinases in kidney homeostasis and diseases

Ciglitazone, a PPARγ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance

Coronary artery atherosclerosis in patients with the initial and the early stage of chronic renal failure

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