Key result
1-Methyl-2-undecyl-4(1H)-quinolone (30-300 nM) inhibited high phosphate-induced calcification of human aortic valve interstitial cells in a concentration-dependent manner by decreasing PiT-1 expression.
MUQ, an evocarpine derivative, attenuates high phosphate-induced calcification of human aortic valve interstitial cells by inhibiting PiT-1 expression, suggesting a potential therapeutic target for calcific aortic stenosis.
May identify PiT-1 as a target in calcific aortic stenosis; leaves open translation from cell culture to patients.
An abnormally high serum phosphate level induces calcific aortic stenosis (CAS), which is characterized by ectopic valve calcification and stenosis of the orifice area. Inhibition of ectopic calcification is a critical function of any internal medical therapy for CAS disease. The aim of the present study was to investigate the inhibitory effects of several derivatives of evocarpine, methanolic extracts from the fruits of Evodia rutaecarpa Bentham (Japanese name: Go-Shu-Yu) on the high phosphate-induced calcification of human aortic valve interstitial cells (HAVICs) obtained from patients with CAS. High phosphate (3.2 mM) concentrations significantly increased the calcification of HAVICs after 7 days of culture. This calcification was completely inhibited in the presence of sodium phosphonoformate (PFA), a selective inhibitor of the type III sodium-dependent phosphate cotransporter (PiT-1). PiT-1 contributes to phosphate uptake, resulting in calcification. 1-Methyl-2-undecyl-4(1H)-quinolone (MUQ; 30-300 nM), but not evocarpine or its derivatives dihydroevocarpine and 1-methyl-2-nonyl-4(1H)-quinolone, inhibited the high phosphate-induced HAVICs calcification in a concentration-dependent manner. Although all of the evocarpine derivatives attenuated alkaline phosphatase activity, only MUQ also decreased PiT-1 gene expression with cellular PiT-1 protein diminution. These results suggest that MUQ mitigated high phosphate-induced HAVICs calcification by inhibiting PiT-1 gene expression.
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Seya et al. (2016) studied Calcific aortic stenosis. 1-Methyl-2-undecyl-4(1H)-quinolone (MUQ) vs. High phosphate alone / other derivatives was evaluated on High phosphate-induced HAVICs calcification and PiT-1 gene expression. 1-Methyl-2-undecyl-4(1H)-quinolone (30-300 nM) inhibited high phosphate-induced calcification of human aortic valve interstitial cells in a concentration-dependent manner by decreasing PiT-1 expression.
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