SNF472, a novel anti-crystallization agent, inhibits induced calcification in an in vitro model of human aortic valve calcification

A Zabirnyk; M D Ferrer; M Bogdanova; M M Pérez; C Salcedo; M-L Kaljusto; J-P E Kvitting; K-O Stensløkken; J Perelló; J Vaage

doi:10.1016/j.vph.2019.106583

SNF472, a novel anti-crystallization agent, inhibits induced calcification in an in vitro model of human aortic valve calcification

Vascul Pharmacol. 2019 Nov-Dec:122-123:106583. doi: 10.1016/j.vph.2019.106583. Epub 2019 Aug 19.

Authors

A Zabirnyk¹, M D Ferrer², M Bogdanova³, M M Pérez⁴, C Salcedo⁴, M-L Kaljusto⁵, J-P E Kvitting⁶, K-O Stensløkken³, J Perelló⁷, J Vaage⁸

Affiliations

¹ Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. Electronic address: arsenii.zabirnyk@medisin.uio.no.
² Sanifit Therapeutics, Palma, Spain; Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, Palma, Spain.
³ Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
⁴ Sanifit Therapeutics, Palma, Spain.
⁵ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cardiothoracic Surgery, Oslo University Hospital, Oslo, Norway.
⁶ Department of Cardiothoracic Surgery, Oslo University Hospital, Oslo, Norway.
⁷ Sanifit Therapeutics, Palma, Spain; Department of Chemistry, University of the Balearic Islands, Palma, Spain.
⁸ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

PMID: 31437530
DOI: 10.1016/j.vph.2019.106583

Abstract

The purpose of the present study was to investigate whether SNF472, the hexasodium salt of myo-inositol hexaphosphate (IP6 or phytate): 1. Inhibits induced calcification in cultured aortic valve interstitial cells (VIC) as an in vitro model of aortic valve stenosis and 2. Whether inhibition is different in VIC obtained from healthy and calcified aortic valves. VIC from healthy (n = 5) and calcified (n = 7) human aortic valves were seeded in basic growth medium, osteogenic differentiation medium alone, or in osteogenic medium with SNF472 (3, 10, and 30 μM) and cultivated for 3 weeks. Calcification was quantified spectrophotometrically after Alizarin Red staining. In VIC from calcified valves, a complete inhibition of calcification was observed with SNF472 concentrations of 10 and 30 μM (p < .01), significantly stronger than in VIC from healthy valves. When SNF472 was added to VIC after 1 week in osteogenic medium, 30 and 100 μM SNF472 inhibited the progression of ongoing calcification by 81 and 100% (p < .01), respectively. The same concentrations of SNF472 given after 2 weeks reduced calcification by 35 and 40% respectively (not significant). SNF472 inhibited both the formation and the progression of calcification with the strongest effect in VIC from calcified valves.

Keywords: Aortic valve stenosis; Calcification inhibition; Phytate; SNF472; Valve interstitial cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aortic Valve / drug effects*
Aortic Valve / metabolism
Aortic Valve / pathology
Aortic Valve Stenosis / drug therapy*
Aortic Valve Stenosis / metabolism
Aortic Valve Stenosis / pathology
Calcium / metabolism*
Case-Control Studies
Cells, Cultured
Crystallization
Disease Progression
Humans
Phytic Acid / pharmacology*
Time Factors

Substances

SNF472
Phytic Acid
Calcium