The Effect Of OxLDL On Heart Valve Interstitial Cells

ObjectiveCalcific aortic valve stenosis is a common disease in the elderly and is characterizedby progressive calcification and fibrous thickening of the valve, but the cellular andmolecular mechanisms are not fully understood. We hypothesized that porcine valveinterstitial cells (ICs) are able to differentiate into osteoblast-like cells through the influenceof oxLDL and that this process can be modulated pharmacologically.Methods(1) The porcine aortic valve interstitial cells were immediately isolated from adultporcine valve leaflets by enzymatic digestion.(2) The porcine aortic valve interstitial cellswere randomly divided into five groups: control group, stimulated by oxLDL, pretreatedwith atorvastatin and oxLDL stimulated group, treated by atorvastatin and solvent controlgroup. Immunocytofluorescent method was used to detect the protein expression of α-SMAand vWF factor. CFDASE was used to detect the aortic valve interstitial cell proliferation.AnnexinV-FITC/PI was used to detect the apoptosis of aortic valve interstitial cell. Theexpression of osteopontin mRNA was detected by RT-PCR. The expression of osteopontinand core binding factor α1(Cbf-α1) was examined by western blot.ResultsQxLDL can induce the apoptosis of porcine aortic valve cells and atorvastatin canreduce the apoptosis of porcine aortic valve interstitial cell induced by oxLDL(P＜0.05). OxLDL can stimulate the proliferation of aortic valve cell and atorvastatin reduce theproliferation of porcine aortic valve interstitial cell induced by oxLDL. OxLDL canup-regulate the expression of osteopontin mRNA, the expression of protein osteopontin andCbf-α1. Atorvastatin can down-regulate the expression of osteopontin mRNA, theexpression of protein osteopontin and Cbf-α1induced by oxLDL.ConclusionOxLDL can stimulate the apoptosis and proliferation of porcine aortic valve cell andatorvastatin can inhibit the apoptosis and proliferation of porcine aortic valve cell inducedby oxLDL. OxLDL can induce osteoblastic differentiation in aortic valve interstitial cells.Aortic valve interstitial cells play important role in the calcification of aortic valve andatorvastatin can prevent the osteoblastic differentiation in aortic valve interstitial cellsinduced by oxLDL.