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

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

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