Urinary Thrombin as a Marker of Glomerular Inflammation Associated with Renal Injury in Type 2 Diabetes.

Glomerular inflammation is a putative aggravation factor for type 2 diabetic nephropathy and urinary thrombin is a novel marker of glomerular inflammation. To clarify the relationship between glomerular inflammation and progression of the nephropathy, we measured urinary thrombin in 118 patients with type 2 diabetic nephropathy at different stages. To investigate the implications of urinary thrombin in the nephropathy, we compared urinary thrombin with expression of tissue factor, the trigger of blood coagulation activation, in glomeruli and with markers of renal injury (estimated glomerular filtration rate (eGFR) and proteinuria). Urinary thrombin was found in 4.9% (3/61), 0.0% (0/12), 29.6% (8/27) and 50.0% (9/18) of patient groups at stages 1, 2, 3 and 4, respectively. Thus, urinary thrombin was negligible in the patients at early stages (stages 1 and 2), but was present predominantly in the patients at advanced stages (stages 3 and 4). Tissue factor was expressed in accumulated macrophages in glomeruli, which indicates that thrombin may be generated in inflamed glomeruli presumably via inflammation-induced activation of the exudated coagulation factors into glomerular tissues and then be excreted in urine. Urinary thrombin was significantly associated with both decreased eGFR and increased proteinuria in type 2 diabetic nephropathy. Therefore, increased urinary thrombin in patients with advanced stages of type 2 diabetic nephropathy suggests that glomerular inflammation may injure the tissues, thereby impairing renal function. Monitoring an effect of anti-diabetic treatments on glomerular inflammation in the patients with type 2 diabetic nephropathy may be a possible application of urinary thrombin.

Amelioration of salvianolic acid C on aortic structure in apolipoprotein E-deficient mice treated with angiotension II.

AIMS: Aortic aneurysm is a disastrous vascular disease with high morbidity and mortality. Matrix metalloproteinases (MMPs), especially MMP-9, is implicated in the development of aortic aneurysm, but the effective MMP inhibitors are far from development. To develop new candidate compound for aortic aneurysm therapy, we evaluated the effects of salvianolic acid C (SalC) against the formation of aortic aneurysm. MATERIALS AND METHODS: Aortic aneurysm was induced by implantation of angiotension II (AngII) minipump in apolipoprotein E-deficient (ApoE-/-) mice. MMPs activity was evaluated by enzyme kinetic analysis in vitro and in-gel gelatin zymography in vivo. The formation of aortic aneurysm was confirmed based on aortic maximum diameter. Hematoxylin and eosin stain was used to evaluate aortic structure, picrosirius red stain was for collagen deposition, and orcein stain was for elastin fragmentation. Macrophage infiltration was detected by CD68 immunohistochemistry. KEY FINDINGS: Firstly, SalC showed significant inhibition on the activity of MMP-2 and MMP-9. Aortic aneurysm was defined as >50% increase in maximum diameter of aorta, and the down-regulated tendency of 20mg/kg SalC against formation of aortic aneurysm was detected. Also, 22.2% rupture was detected in ApoE-/- mice, while no rupture of aortic aneurysm was found with 20mg/kg SalC treatment. Then, SalC was detected to maintain the integrity of aortic structure and protect elastin against fragmentation. Finally, SalC considerably inhibited infiltration of macrophage in the injury site of aorta. SIGNIFICANCE: SalC significantly ameliorated the progression of aortic aneurysm in ApoE-/- mice, and held great potential for aortic aneurysm therapy.