Except for the standard aortic valve replacement,no effective medical treatment is available to prevent or delay calcific aortic valve disease(CAVD)progression.Recently,macrophages and high-mobility group box 1(HMGB1)...Except for the standard aortic valve replacement,no effective medical treatment is available to prevent or delay calcific aortic valve disease(CAVD)progression.Recently,macrophages and high-mobility group box 1(HMGB1)are the most intriguing candidates in various inflammatory disorders.However,the association between serum HMGB1,CAVD,and macrophage polarization remains unclear.Therefore,we examined whether the level of serum HMGB1 is clinically associated with aortic valve calcification and whether HMGB1 treatment can promote macrophage differentiation toward M1 or M2 phenotype.This experimental study included 19 CAVD patients and 20 healthy controls whose serum HMGB1 levels were examined by ELISA assay.THP-1 macrophage polarization system was established to test the polarization capability of HMGB1 treatment.The results showed that serum levels of HMGB1 were significantly reduced in patients with CAVD.HMGB1 treatment promoted M2 macrophage polarization but not M1 phenotype with increased IL-10 expression and reduced inducible nitric oxide synthase(iNOS)expression.Our findings suggest that serum HMGB1 is negatively associated with the development of aortic valve calcification,and HMGB1 treatment may facilitate M2 macrophage polarization for reducing aortic valve calcification.展开更多
Cardiac valve calcification is a common disease,especially among the elderly.Calcification can affect valve function and cause heart failure and sudden death(Adler et al.,2002).Aortic valve calcification is alsorelate...Cardiac valve calcification is a common disease,especially among the elderly.Calcification can affect valve function and cause heart failure and sudden death(Adler et al.,2002).Aortic valve calcification is alsorelated to arteriosclerosis and coronary heart disease(Rashedi et al.,2015).However,the origin of valve calcification is still unclear.This study characterized the展开更多
Mitral annular calcification (MAC) and aortic valve calcification (AVC) are the most common valvular and perivalvular abnormalities in patients with chronic kidney disease (CKD). Both MAC and AVC occur at a younger ag...Mitral annular calcification (MAC) and aortic valve calcification (AVC) are the most common valvular and perivalvular abnormalities in patients with chronic kidney disease (CKD). Both MAC and AVC occur at a younger age in CKD patients than in the general population. AVC progresses to aortic stenosis and mild aortic stenosis progresses to severe aortic stenosis at a more rapid rate in patients with CKD than in the general population. The use of calcium-free phosphate binders in such patients may reduce the calcium burden in valvular and perivalvular structures and retard the rate of progression of aortic stenosis. Despite high rates of morbidity and mortality, the prognosis associated with valve surgery in patients with CKD is better than without valve surgery. Infective endocarditis remains an important complication of CKD, particularly in those treated with hemodialysis.展开更多
目的探讨老年钙化性心脏瓣膜病患者颈动脉斑块积分(Crouse积分)、内膜中层厚度(intima media thickness,IMT)与瓣膜钙化程度的关系。方法回顾性分析2020年4月至2023年3月收治的106例老年钙化性心脏瓣膜病患者的临床资料(观察组)。另选...目的探讨老年钙化性心脏瓣膜病患者颈动脉斑块积分(Crouse积分)、内膜中层厚度(intima media thickness,IMT)与瓣膜钙化程度的关系。方法回顾性分析2020年4月至2023年3月收治的106例老年钙化性心脏瓣膜病患者的临床资料(观察组)。另选择90例颈动脉粥样硬化的非心脏瓣膜病患者作为对照组1、选取95例非老年钙化性心脏瓣膜病患者作为对照组2。单因素方差分析检验三组Crouse积分、IMT、管腔狭窄程度及老年钙化性心脏瓣膜病不同心瓣膜钙化程度患者Crouse积分、IMT。Pearson分析Crouse积分、IMT与心瓣膜钙化程度的相关性;受试者工作特征(ROC)曲线分析Crouse积分、IMT对老年钙化性心脏瓣膜病患者瓣膜钙化的预测价值。结果观察组Crouse积分、IMT、管腔狭窄程度均明显高于对照组1和对照组2(P<0.05)。老年钙化性心脏瓣膜病不同心瓣膜钙化程度患者Crouse积分、IMT比较:1级<2级<3级(P<0.05)。相关性分析结果显示,Crouse积分、IMT与老年钙化性心脏瓣膜病瓣膜钙化程度均呈明显正相关关系(r=0.585、0.623,P<0.05)。绘制Crouse积分、IMT预测老年钙化性心脏瓣膜病患者瓣膜钙化的ROC曲线示,Crouse积分、IMT联合预测的AUC为0.802(95%CI为0.738~0.867),明显高于各指标单一预测的AUC,最佳诊断敏感度和特异度分别为0.887、0.794(P<0.05)。结论老年钙化性心脏瓣膜病患者Crouse积分、IMT存在异常增高,且与瓣膜钙化程度呈正相关,测量上述指标有助于对心脏瓣膜钙化程度进行评估。展开更多
Objective:Calcific aortic valve disease(CAVD)affects millions of elderly people,and there is currently no effective way to stop or slow down its progression.Therefore,exploring the pathogenesis of CAVD is very importa...Objective:Calcific aortic valve disease(CAVD)affects millions of elderly people,and there is currently no effective way to stop or slow down its progression.Therefore,exploring the pathogenesis of CAVD is very important for prevention and treatment.Cartilage oligomeric matrix protein(COMP)have important role in cell phenotype change.This study is aimed to confirm whether COMP participate in CAVD and try to find the possible mechanisms.Methods:Human aortic valve tissues from Nanjing First Hospital(CAVD group,n=20;control group,n=11)were harvested.The expression level of COMP was tested by western blot and immunohistochemistry.Dual immunofluorescence staining was used for locating COMP.Bone morphogenetic protein-2(BMP2)signalling were tested by western blot.The animal model was also used to detect COMP level by immunohistochemistry.Results:The results showed that the expression level of COMP was significantly increased in the calcific valve samples when compared with that of the control valve(P<0.05);COMP was expressed near the calcific nodules and co-localized with a-smooth muscle actin(a-SMA).The protein levels of BMP2 and p-Smads 1/5/9 were markedly more highly expressed in the CAVD group than the control group(P<0.05).Furthermore,immunofluorescence detection showed that COMP and BMP2 were co-located in calcific valves.Conclusions:The above results suggested that upregulation of COMP and BMP2 may be associated with aortic valve calcification and that COMP may become a potential therapeutic target in human CAVD.展开更多
文摘Except for the standard aortic valve replacement,no effective medical treatment is available to prevent or delay calcific aortic valve disease(CAVD)progression.Recently,macrophages and high-mobility group box 1(HMGB1)are the most intriguing candidates in various inflammatory disorders.However,the association between serum HMGB1,CAVD,and macrophage polarization remains unclear.Therefore,we examined whether the level of serum HMGB1 is clinically associated with aortic valve calcification and whether HMGB1 treatment can promote macrophage differentiation toward M1 or M2 phenotype.This experimental study included 19 CAVD patients and 20 healthy controls whose serum HMGB1 levels were examined by ELISA assay.THP-1 macrophage polarization system was established to test the polarization capability of HMGB1 treatment.The results showed that serum levels of HMGB1 were significantly reduced in patients with CAVD.HMGB1 treatment promoted M2 macrophage polarization but not M1 phenotype with increased IL-10 expression and reduced inducible nitric oxide synthase(iNOS)expression.Our findings suggest that serum HMGB1 is negatively associated with the development of aortic valve calcification,and HMGB1 treatment may facilitate M2 macrophage polarization for reducing aortic valve calcification.
基金supported by the National Natural Science Foundation of China(Grant NO.40972210,41272048)
文摘Cardiac valve calcification is a common disease,especially among the elderly.Calcification can affect valve function and cause heart failure and sudden death(Adler et al.,2002).Aortic valve calcification is alsorelated to arteriosclerosis and coronary heart disease(Rashedi et al.,2015).However,the origin of valve calcification is still unclear.This study characterized the
文摘Mitral annular calcification (MAC) and aortic valve calcification (AVC) are the most common valvular and perivalvular abnormalities in patients with chronic kidney disease (CKD). Both MAC and AVC occur at a younger age in CKD patients than in the general population. AVC progresses to aortic stenosis and mild aortic stenosis progresses to severe aortic stenosis at a more rapid rate in patients with CKD than in the general population. The use of calcium-free phosphate binders in such patients may reduce the calcium burden in valvular and perivalvular structures and retard the rate of progression of aortic stenosis. Despite high rates of morbidity and mortality, the prognosis associated with valve surgery in patients with CKD is better than without valve surgery. Infective endocarditis remains an important complication of CKD, particularly in those treated with hemodialysis.
文摘目的探讨老年钙化性心脏瓣膜病患者颈动脉斑块积分(Crouse积分)、内膜中层厚度(intima media thickness,IMT)与瓣膜钙化程度的关系。方法回顾性分析2020年4月至2023年3月收治的106例老年钙化性心脏瓣膜病患者的临床资料(观察组)。另选择90例颈动脉粥样硬化的非心脏瓣膜病患者作为对照组1、选取95例非老年钙化性心脏瓣膜病患者作为对照组2。单因素方差分析检验三组Crouse积分、IMT、管腔狭窄程度及老年钙化性心脏瓣膜病不同心瓣膜钙化程度患者Crouse积分、IMT。Pearson分析Crouse积分、IMT与心瓣膜钙化程度的相关性;受试者工作特征(ROC)曲线分析Crouse积分、IMT对老年钙化性心脏瓣膜病患者瓣膜钙化的预测价值。结果观察组Crouse积分、IMT、管腔狭窄程度均明显高于对照组1和对照组2(P<0.05)。老年钙化性心脏瓣膜病不同心瓣膜钙化程度患者Crouse积分、IMT比较:1级<2级<3级(P<0.05)。相关性分析结果显示,Crouse积分、IMT与老年钙化性心脏瓣膜病瓣膜钙化程度均呈明显正相关关系(r=0.585、0.623,P<0.05)。绘制Crouse积分、IMT预测老年钙化性心脏瓣膜病患者瓣膜钙化的ROC曲线示,Crouse积分、IMT联合预测的AUC为0.802(95%CI为0.738~0.867),明显高于各指标单一预测的AUC,最佳诊断敏感度和特异度分别为0.887、0.794(P<0.05)。结论老年钙化性心脏瓣膜病患者Crouse积分、IMT存在异常增高,且与瓣膜钙化程度呈正相关,测量上述指标有助于对心脏瓣膜钙化程度进行评估。
基金the general program of Science and Technology Development Foundation of Nanjing Medical University(No.NMUB2018314)Jiangsu Provincial Key Medical Discipline(Laboratory)(ZDXKA2016021).
文摘Objective:Calcific aortic valve disease(CAVD)affects millions of elderly people,and there is currently no effective way to stop or slow down its progression.Therefore,exploring the pathogenesis of CAVD is very important for prevention and treatment.Cartilage oligomeric matrix protein(COMP)have important role in cell phenotype change.This study is aimed to confirm whether COMP participate in CAVD and try to find the possible mechanisms.Methods:Human aortic valve tissues from Nanjing First Hospital(CAVD group,n=20;control group,n=11)were harvested.The expression level of COMP was tested by western blot and immunohistochemistry.Dual immunofluorescence staining was used for locating COMP.Bone morphogenetic protein-2(BMP2)signalling were tested by western blot.The animal model was also used to detect COMP level by immunohistochemistry.Results:The results showed that the expression level of COMP was significantly increased in the calcific valve samples when compared with that of the control valve(P<0.05);COMP was expressed near the calcific nodules and co-localized with a-smooth muscle actin(a-SMA).The protein levels of BMP2 and p-Smads 1/5/9 were markedly more highly expressed in the CAVD group than the control group(P<0.05).Furthermore,immunofluorescence detection showed that COMP and BMP2 were co-located in calcific valves.Conclusions:The above results suggested that upregulation of COMP and BMP2 may be associated with aortic valve calcification and that COMP may become a potential therapeutic target in human CAVD.
