Vorapaxar treatment reduces mesangial expansion in streptozotocin-induced diabetic nephropathy in mice

Oncotarget
Maaike WaasdorpC Arnold Spek

Abstract

Twenty years after the onset of diabetes, up to 40% of patients develop diabetic nephropathy. Protease-activated receptor-1 (PAR-1) has recently been shown to aggravate the development of experimental diabetic nephropathy. PAR-1 deficient mice develop less albuminuria and glomerular lesions and PAR-1 stimulation induces proliferation and fibronectin production in mesangial cells in vitro. Vorapaxar is a clinically available PAR-1 inhibitor which is currently used for secondary prevention of ischemic events. The aim of this study was to investigate in a preclinical setting whether vorapaxar treatment may be a novel strategy to reduce diabetes-induced kidney damage. While control treated diabetic mice developed significant albuminuria, mesangial expansion and glomerular fibronectin deposition, diabetic mice on vorapaxar treatment did not show any signs of kidney damage despite having similar levels of hyperglycemia. These data show that PAR-1 inhibition by vorapaxar prevents the development of diabetic nephropathy in this preclinical animal model for type I diabetes and pinpoint PAR-1 as a novel therapeutic target to pursue in the setting of diabetic nephropathy. 22 C57Bl/6 mice were made diabetic using multiple low-dose streptoz...Continue Reading

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Citations

May 23, 2019·Current Hypertension Reports·Alexander StaruschenkoOleg Palygin
Jul 10, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maaike WaasdorpC Arnold Spek
Mar 24, 2020·American Journal of Physiology. Renal Physiology·Shohei MitsuiNobuyuki Takahashi
Jul 28, 2020·Journal of the American Society of Nephrology : JASN·Thati MadhusudhanBerend Isermann
Jan 17, 2020·Nature Reviews. Nephrology·Sydney C W Tang, Wai Han Yiu
Nov 19, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Zhuang-Zhuang TangYao-Wu Liu

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Methods Mentioned

BETA
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Software Mentioned

GraphPad Prism
Image Pro Plus
ImageJ

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