The search result changed since you submitted your search request. Documents might be displayed in a different sort order.
  • search hit 7 of 144
Back to Result List

The matrix metalloproteinases 2 and 9 initiate uraemic vascular calcifications

  • 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 almostThe 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 mRNA expression blocked calcification of murine VSMC induced by calcification medium (CM). In contrast to MMP inhibition, recombinant MMP-2 or MMP-9 enhanced CM-induced calcifications and the secretion of gelatinases. These data indicate that both gelatinases provide essential signals for phenotypic VSMC conversion, matrix remodelling and the initiation of vascular calcification. Their inhibition seems a promising strategy in the prevention of vascular calcifications.show moreshow less

Export metadata

Additional Services

Search Google Scholar Statistics
Metadaten
Author details:Eva Hecht, Christian Freise, Karoline von WebskyORCiDGND, Hamoud Nasser, Nadja Kretzschmar, Philipp Stawowy, Berthold HocherORCiDGND, Uwe Querfeld
DOI:https://doi.org/10.1093/ndt/gfv321
ISSN:0931-0509
ISSN:1460-2385
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/26333546
Title of parent work (English):Nephrology, dialysis, transplantation
Publisher:Oxford Univ. Press
Place of publishing:Oxford
Publication type:Article
Language:English
Year of first publication:2016
Publication year:2016
Release date:2020/03/22
Tag:chronic kidney disease; matrix metalloproteinases; vascular calcification; vascular smooth muscle cells
Volume:31
Number of pages:9
First page:789
Last Page:797
Funding institution:Peter Stiftung fur die Naturwissenschaften; Berliner Sparkassenstiftung Medizin; Charite Funds for Research; Else Kroner-Fresenius Stiftung [2011_A19]
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
Peer review:Referiert
Accept ✔
This website uses technically necessary session cookies. By continuing to use the website, you agree to this. You can find our privacy policy here.