ADAMTS13 Retards Progression of Diabetic Nephropathy by Inhibiting Intrarenal Thrombosis in Mice

Arteriosclerosis, Thrombosis, and Vascular Biology
Nirav DhaneshaA K Chauhan

Abstract

ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I repeats-13) prevents microvascular thrombosis by cleaving prothrombogenic ultralarge von Willebrand factor (VWF) multimers. Clinical studies have found association between reduced ADAMTS13-specific activity, ultralarge VWF multimers, and thrombotic angiopathy in patients with diabetic nephropathy. It remains unknown, however, whether ADAMTS13 deficiency or ultralarge VWF multimers have a causative effect in diabetic nephropathy. The extent of renal injury was evaluated in wild-type (WT), Adamts13-/- and Adamts13-/-Vwf-/- mice after 26 weeks of streptozotocin-induced diabetic nephropathy. We found that WT diabetic mice exhibited low plasma ADAMTS13-specific activity and increased VWF levels (P<0.05 versus WT nondiabetic mice). Adamts13-/- diabetic mice exhibited deterioration of kidney function (increased albuminuria, plasma creatinine, and urea; P<0.05 versus WT diabetic mice), independent of hyperglycemia and hypertension. Deterioration of kidney function in Adamts13-/- diabetic mice was concomitant with aggravated intrarenal thrombosis (assessed by plasminogen activator inhibitor, VWF, fibrin(ogen), and CD41-positive microthrombi), increased mesangial cell...Continue Reading

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Citations

Dec 29, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Ann Marie Schmidt
Nov 22, 2018·American Journal of Physiology. Renal Physiology·Suhan ZhouEn Yin Lai
Jun 27, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Henry H RuizAnn Marie Schmidt
Oct 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Hong S LuAlan Daugherty

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