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[Abstract] Calcific aortic valve disease is a process involving complex pathological changes such as endothelial injury, chronic inflammation, extracellular matrix remodeling, cell phenotype differentiation and apoptosis. The aortic valve is mainly composed of internal valve interstitial cells and external valve endothelial cells, and they are all involved in the pathological process of calcific aortic valve disease. Non-coding RNA participates in the pathophysiological process of cardiovascular disease mainly through post-transcriptional regulation mechanism, and may play an important role in the development and progression of calcific aortic valve disease.
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Objective@# To explore the role of lipopolysaccharide（LPS）in the pathogenesis of calcific aortic valve disease（CAVD）by detecting the expression of inflammatory factors in aortic valve interstitial cells（AVICs），and the expression of interleukin-6（IL-6），interleukin-8（IL-8），monocyte chemoattractant protein-1（MCP-1）after silencing pentraxin 3（PTX3）gene，to test the effect of PTX3 on the pathophysiological process of CAVD. @*Methods@#We obtained aortic valves for immunohistochemistry staining from 12 patients with CAVD，and from 12 patients without aortic valve disease receiving heart transplant operation as controlAVICs were cultured in vitro，different concentrations of LPS（0，50，100，200 ng/mL）treated cells for 24 h，and then the expression levels of IL-6，IL-8 and MCP-1 were analyzed by real-time polymerase chain reaction（real-time PCR）. After AVICs were transfected with PTX3 siRNA for 48 h to knockdown the expression of PTX3 protein，PTX3 was tested by Western blotting. The levels of IL-6，IL-8 and MCP-1 were detected by real-time PCR 24 h after treatment with LPS（100 ng/mL）in AVICs with PTX3 siRNA transfection. @*Results@#The calcific aortic valves significantly expressed PTX3 as compared with control.LPS dose-dependently increased IL-6，IL-8 and MCP-1 in AVICs. Compared with control groups，100 ng/mL LPS significantly increased IL-6，IL-8 and MCP-1 mRNA（P<0.05，P<0.01）. PTX3 siRNA markedly decreased the levels of PTX3 protein compared with control groups（P<0.01）. Levels of IL-6，IL-8 and MCP-1 were significantly reduced in LPS plus PTX3 siRNA group compared with controls（all P<0.05）.@*Conclusion@#The calcific aortic valves have a higher level of PTX3 than control valves.LPS stimulates the expression of IL-6，IL-8 and MCP-1 in AVICs，but silencing PTX3 gene significantly inhibits LPS-stimulated expression of IL-6，IL-8 and MCP-1. PTX3 may play a role in CAVD pathogenesis by regulating expression of inflammatory factors
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Objective:To evaluate the association between the level of plasma proprotein convertase subtilisin/Kexin 9 (PCSK9) with incidence and severity of calcified aortic valve disease(CAVD).Methods:We prospectively recruited 120 CAVD patients with at least increased echo density and 40 control patients by transthoracic echocardiography.All patients were grouped by CT quantitative scoring system:aortic valve calcification (AVC)1,2,3 and 4.Calcium score of aortic valve were calculated.Total cholesterol (TC),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C),triglyceride (TG), carrying lipoprotein A1 (apo A1) and apolipoprotein B (apo B),lipoprotein (a) {LP (a)} and hypersensitive C-reactive protein (hsCRP) were detected by biochemical analyzer.Plasma PCSK9 levels were measured by enzyme-linked immunosorbent assay.The re-lationship between AVC and plasma PCSK9 level,blood lipid,Apo A1,Apo B and hsCRP was analyzed.Results:The data indicated that Apo,B Lp(a) and LDL-C levels in AVC2-4 level was significantly higher than that of AVC1(P<0.05),while TG,APO,A1 HDL-C and hsCRP were not different significantly in the four groups.The levels of TC in group AVC3 and AVC4 were significantly higher than those in group AVC1(P<0.05).At the same time,the patients of grade AVC2-4 have higher level of plasma PCSK9 than patients of group AVC1(P<0.05).Correlation analysis was performed and aortic valve calcium score were significantly correlated with TC (r=0.248,P=0.026),LDL-C (r=0.222,P=0.048),Lp(a) (r=0.276,P=0.013),Apo A1(r=0.245,P=0.012),Apo B(r=0.212, P=0.019) and PCSK9(r=0.309,P=0.005) in all study subjects.PCSK9 was positively correlated with TC,LDL,LP (a),Apo A1, Apo,and no correlation with hsCRP (B).Conclusion:The level of PCSK9 in CAVD patients was significantly higher than that in control group.And there is an association of PCSK9 levels with the presence of CAVD,however.
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The incidence of calcific aortic valve disease (CAVD) has increased dramatically as a result of the decline in rheumatic fever and the increase of the aging population, and by now CAVD has become the most common cardiac valve disease in the elderly in China. CAVD used to be thought as an irreversible passive process relating to valve degeneration and calcium accumulation. However, latest research has shown that CAVD is a complex active process, which involving vascular endothelial injury, lipid infiltration, chronic inflammation, matrix remodeling, cell differentiation, progressive bone formation, and neovascularization. Besides, genetic mutation also play a significant role in the process. Novel therapeutic target and technology such as transcatheter aortic valve implantation have been developed, which casts new lights on CAVD prevention and treatment. This review focused on the current understanding of the pathogenesis and future diagnosis/ therapies of CAVD.
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To observe the biological characteristics of valvular interstitial cells in calcific aortic valve disease (CAVD), so as to lay a foundation for future study. Methods Tissue culture inoculation and immunomagnetic bead separation method were used to isolate the valvular interstitial cells from the normal aortic valves and CAVD valves. The morphological and behavioral characteristics of the isolated valvular interstitial cells were observed. Immunocytochemistry and flow cytometry an alysis were employed to determine cellular immunophenotype. Results Compared to normal valvular interstitial cells, CAVD valvular interstitial cells displayed a myofibroblast- and osteoblast- like morphology. When the cell density reached acertain level, they spontaneously retracted from the neighboring areas and grouped into aggregates, forming calcific nodules. Furthermore, CAVD valvular interstitial cells cultured in vitro were positive for myofibroblast markera α-SMA and osteoblast marker alkaline phosphatase. Conclusion Biological characteristic change of CAVD valvular interstitial cells might be the major reason for the thickening, calcification, and commissural fusion in CAVD valvular samples.