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The Ryanodine Receptor Contributes to the Lysophosphatidylcholine-Induced Mineralization in Valvular Interstitial Cells.
Cardiovascular Engineering and Technology ( IF 1.6 ) Pub Date : 2020-04-30 , DOI: 10.1007/s13239-020-00463-1 Reid L Wilson 1, 2 , Christopher B Sylvester 1, 2 , Dena C Wiltz 1 , Aditya Kumar 1 , Tahir H Malik 1 , Joel D Morrisett 3 , K Jane Grande-Allen 1
中文翻译:
Ryanodine 受体有助于瓣膜间质细胞中溶血磷脂酰胆碱诱导的矿化。
更新日期:2020-04-30
Cardiovascular Engineering and Technology ( IF 1.6 ) Pub Date : 2020-04-30 , DOI: 10.1007/s13239-020-00463-1 Reid L Wilson 1, 2 , Christopher B Sylvester 1, 2 , Dena C Wiltz 1 , Aditya Kumar 1 , Tahir H Malik 1 , Joel D Morrisett 3 , K Jane Grande-Allen 1
Affiliation
Purpose
Fibrocalcific aortic valve disease (CAVD) is caused by the deposition of calcific nodules in the aortic valve leaflets, resulting in progressive loss of function that ultimately requires surgical intervention. This process is actively mediated by the resident valvular interstitial cells (VICs), which, in response to oxidized lipids, transition from a quiescent to an osteoblast-like state. The purpose of this study was to examine if the ryanodine receptor, an intracellular calcium channel, could be therapeutically targeted to prevent this phenotypic conversion.Methods
The expression of the ryanodine receptor in porcine aortic VICs was characterized by qRT-PCR and immunofluorescence. Next, the VICs were exposed to lysophosphatidylcholine, an oxidized lipid commonly found in low-density lipoprotein, while the activity of the ryanodine receptor was modulated with ryanodine. The cultures were analyzed for markers of cellular mineralization, alkaline phosphatase activity, proliferation, and apoptosis.Results
Porcine aortic VICs predominantly express isoform 3 of the ryanodine receptors, and this protein mediates the cellular response to LPC. Exposure to LPC caused elevated intracellular calcium concentration in VICs, raised levels of alkaline phosphatase activity, and increased calcific nodule formation, but these changes were reversed when the activity of the ryanodine receptor was blocked.Conclusions
Our findings suggest blocking the activity of the ryanodine receptor can attenuate the valvular mineralization caused by LPC. We conclude that oxidized lipids, such as LPC, play an important role in the development and progression of CAVD and that the ryanodine receptor is a promising target for pharmacological intervention.中文翻译:
Ryanodine 受体有助于瓣膜间质细胞中溶血磷脂酰胆碱诱导的矿化。