The matrix metalloproteinases 2 and 9 initiate uraemic vascular calcifications

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
Eva HechtUwe Querfeld

Abstract

The matrix metalloproteinases (MMP) MMP-2 and MMP-9 are physiological regulators of vascular remodelling. Their dysregulation could contribute to vascular calcification. We examined the role of the MMP-2 and MMP-9 in uraemic vascular calcification in vivo and in vitro. The impact of pharmacological MMP inhibition on the development of media calcifications was explored in an aggressive animal model of uraemic calcification. In addition, the selective effects of addition and inhibition, respectively, of MMP-2 and MMP-9 on calcium-/phosphate-induced calcifications were studied in a murine cell line of vascular smooth muscle cells (VSMCs). High-dose calcitriol treatment of uraemic rats given a high phosphate diet induced massive calcifications, apoptosis and increased gene expressions of MMP-2, MMP-9 and of osteogenic transcription factors and proteins in aortic VSMC. The MMP inhibitor doxycycline prevented the VSMC transdifferentiation to osteoblastic cells, suppressed transcription of mediators of matrix remodelling and almost completely blocked aortic calcifications while further increasing apoptosis. Similarly, specific inhibitors of either MMP-2 or -9, or of both gelatinases (Ro28-2653) and a selective knockdown of MMP-2/-9 mR...Continue Reading

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Citations

Oct 8, 2016·BMC Cardiovascular Disorders·Christian FreiseUwe Querfeld
Apr 16, 2019·Current Opinion in Nephrology and Hypertension·Jakob VoelklIoana Alesutan
Dec 17, 2017·Pharmacological Reviews·Sébastien FoulquierW Matthijs Blankesteijn
Mar 20, 2019·Cellular and Molecular Life Sciences : CMLS·Jakob VoelklIoana Alesutan
Feb 7, 2017·BioMed Research International·Wenhong JiangXiao Qin
Nov 26, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Aoran HuangLi Yao
Dec 24, 2019·Kidney International·Anique D Ter BraakeJeroen H F de Baaij
Feb 2, 2021·Korean Circulation Journal·Hae Young LeeSungha Park
Feb 9, 2021·Frontiers in Cell and Developmental Biology·Liangjun JiangZhijun Pan
Nov 25, 2020·Molecular Therapy. Nucleic Acids·Nakwon ChoeHyun Kook
Dec 28, 2019·Vascular Pharmacology·Samuel O OlapojuXoan Le Thi
Jul 3, 2021·Journal of Personalized Medicine·Yana V PolonskayaYulia I Ragino
Jun 12, 2019·Kidney & Blood Pressure Research·Oskar ZakiyanovVladimír Tesař

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