Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(...Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(COMP),as a component of the vascular matrix,has been found to be an inhibitor of arterial calcification in basic studies.However,there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis(MHD)patients.The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people.MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events(MACEs),which were defined as a combined end point of new onset angina pectoris,nonfatal myocardial infarction,heart failure,coronary artery revascularization,hospitalization due to angina pectoris and all-cause deaths.The CAC score was calculated based on computed tomography scans.Results The serum COMP level in MHD patients was significantly higher than that in the general population[984.23(248.43-1902.61)ng/mL vs.219.01(97.26-821.92)ng/mL,P<0.01].Serum COMP levels were positively correlated with CAC(r=0.313,P=0.021)and serum parathyroid hormone in MHD patients(r=0.359,P<0.01).Linear regression suggested that after adjusting for age,fasting blood glucose(Glu)and glycosylated hemoglobin(HbAlc),CAC score was an independent predictor in the final model for COMP level(β=0.424,t=3.130,P<0.01).The receiver operating characteristic(ROC)curve showed that COMP≥994 mg/mL had 68.0%sensitivity and 72.4%specificity for the prediction of severe CAC[area under the curve(AUC):0.674,P=0.030,95%CI:0.526-0.882].After a median follow-up of 16 months(8-24 months),there was no difference in the incidence rate of MACEs between the upper,middle and lower serum COMP groups.Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls.The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients.However,there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.展开更多
Background Cartilage oligomeric matrix protein （COMP） is mainly found in the skeletal system and vascular smooth muscle cells. Recent researches showed that it had a protective function on blood vessels and could al...Background Cartilage oligomeric matrix protein （COMP） is mainly found in the skeletal system and vascular smooth muscle cells. Recent researches showed that it had a protective function on blood vessels and could also inhibit vascular calcification. We investigated the serum COMPs in coronary heart disease （CHD） patients, and the relationship between serum COMP and the calcification of coronary artery. Methods A total of 233 consecutive chest pain patients who first underwent coronary angiography followed by multi-slice computed to- mography （MSCT） within six months were recruited and divided into two groups according to the coronary angiography luminal diameter narrowing percentages： CHD group （diameter narrowing 〉 50%, n = 194） and control group （diameter narrowing 〈 50%, n = 39）. The Gen- sini score, Syntax score and coronary artery calcium score （CACs） were calculated. The serum COMP level was determined using ELISA. Results The levels of COMP were significantly higher in the CHD group than in the control group 155.7 （124.5-194.5） ng/mL vs. 128.4 （113.0-159.9） ng/mL, P = 0.019. There were no correlation between COMP, Gensini score, Syntax score, severity of coronary stenosis and the number of coronary artery with stenosis 〉 50%. The serum COMP was correlated with age （r = 0.294, P 〈 0.001）, fasting glucose （r = 0.163, P = 0.015）, HbAlc （r = 0.194, P = 0.015） and CACs （r = 0.137, P = 0.037）. Stepwise linear regression analysis showed that COMP level and age were independent predictors of CACs in the CHD patients （fl = 0.402, t = 2.612, P = 0.015; fl = 0.472, t = 3.077, P = 0.005）. Performance of COMP for predicting CHD was shown as area under curve （AUC）： 0.632, 95% CI： 0.549-0.715 and upper tertile CACs was AUC： 0.602, 95% CI： 0.5264）.678 in receiver operating characteristic （ROC） curve analysis. Conclusion Calcification of coronary artery was an independent predictor of serum COMPs.展开更多
Serum levels of cartilage oligomeric matrix protein(COMP) has been presented as a biomarker of liver fibrosis in several cross-sectional studies. COMP is also an essential mediator in carcinoma development and has als...Serum levels of cartilage oligomeric matrix protein(COMP) has been presented as a biomarker of liver fibrosis in several cross-sectional studies. COMP is also an essential mediator in carcinoma development and has also been associated with hepatocellular carcinoma. We present a prospective analysis of this biomarker in38 patients with chronic hepatitis C who were subject to eradication therapy with direct acting antivirals. We confirm previous studies associating COMP elevation with liver cirrhosis. We also show how viral levels are correlated with COMP at baseline. In our prospective analysis, we report that successful eradication of hepatitis C results in improvement in liver stiffness and laboratory liver function tests at 1 year follow-up. In contrast, median COMP-levels remain unchanged during the study period. We conclude that the biomarker potential of COMP in the prospective evaluation of liver diseases, remains to be elucidated.展开更多
Background Pseudoachondroplasia （PSACH） is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein （COMP）.Clinical diagnosis of PSACH is based primaril...Background Pseudoachondroplasia （PSACH） is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein （COMP）.Clinical diagnosis of PSACH is based primarily on family history, physical examination, and radiographic evaluation.There is evidence that decreased serum COMP concentration may serve as a diagnostic marker in PSACH.Here, we investigated the role of this gene and the serum COMP concentration in Chinese patients with PSACH.Methods A family with three patients and a sporadic case were recruited.Genomic and phenotypic data were recorded.The diagnosis of PSACH was made on the base of clinical evaluation.The genomic DNA was extracted from peripheral blood leukocytes.The 8-19 exons and flanking intron-exon boundary sequences of COMP were amplified by polymerase chain reaction （PCR） and screened for mutation by direct DNA sequencing.Serum COMP concentrations of 4 patients and age-compatible control group of 20 unrelated healthy subjects were analyzed on the basis of an ELISA Kit for human cartilage oligomeric matrix protein.Results A deletion （c.1447-1455del） was identified in exon 13 in the sporadic case.The mean serum COMP concentrations of four patients （3.12±2.28） were significantly lower than those of control group （10.86±2.21, P 〈0.05）.There was no overlap in the distribution of serum COMP concentration between PSACH patients and controls.Conclusions Mutations in COMP gene are responsible for the PSACH.Serum COMP concentration may be suggested as an additional diagnostic marker to aid clinical findings in suspected cases of PSACH.展开更多
Background Multiple epiphysis dysplasia （MED） is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined.cases, mutations have been identified in the gene encoding c...Background Multiple epiphysis dysplasia （MED） is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined.cases, mutations have been identified in the gene encoding cartilage algometric matrix protein （ COMP）. Methods Five patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members. Results We have identified a novel mutation in axon 14 of COMP gene in the family. Conclusions This mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.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
基金supported by the National Natural Science Foundation of China(81400262)the Backbone Fund of Peking University Third Hospital(Y72497-04)
文摘Background Coronary artery calcification(CAC)is common in end-stage renal disease(ESRD)patients,and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients.Cartilage oligomeric matrix protein(COMP),as a component of the vascular matrix,has been found to be an inhibitor of arterial calcification in basic studies.However,there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis(MHD)patients.The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.Methods Serum COMP levels were compared between 54 MHD patients and 66 healthy people.MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events(MACEs),which were defined as a combined end point of new onset angina pectoris,nonfatal myocardial infarction,heart failure,coronary artery revascularization,hospitalization due to angina pectoris and all-cause deaths.The CAC score was calculated based on computed tomography scans.Results The serum COMP level in MHD patients was significantly higher than that in the general population[984.23(248.43-1902.61)ng/mL vs.219.01(97.26-821.92)ng/mL,P<0.01].Serum COMP levels were positively correlated with CAC(r=0.313,P=0.021)and serum parathyroid hormone in MHD patients(r=0.359,P<0.01).Linear regression suggested that after adjusting for age,fasting blood glucose(Glu)and glycosylated hemoglobin(HbAlc),CAC score was an independent predictor in the final model for COMP level(β=0.424,t=3.130,P<0.01).The receiver operating characteristic(ROC)curve showed that COMP≥994 mg/mL had 68.0%sensitivity and 72.4%specificity for the prediction of severe CAC[area under the curve(AUC):0.674,P=0.030,95%CI:0.526-0.882].After a median follow-up of 16 months(8-24 months),there was no difference in the incidence rate of MACEs between the upper,middle and lower serum COMP groups.Conclusions Our study found that MHD patients have higher levels of circulating COMP than controls.The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients.However,there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.
文摘Background Cartilage oligomeric matrix protein （COMP） is mainly found in the skeletal system and vascular smooth muscle cells. Recent researches showed that it had a protective function on blood vessels and could also inhibit vascular calcification. We investigated the serum COMPs in coronary heart disease （CHD） patients, and the relationship between serum COMP and the calcification of coronary artery. Methods A total of 233 consecutive chest pain patients who first underwent coronary angiography followed by multi-slice computed to- mography （MSCT） within six months were recruited and divided into two groups according to the coronary angiography luminal diameter narrowing percentages： CHD group （diameter narrowing 〉 50%, n = 194） and control group （diameter narrowing 〈 50%, n = 39）. The Gen- sini score, Syntax score and coronary artery calcium score （CACs） were calculated. The serum COMP level was determined using ELISA. Results The levels of COMP were significantly higher in the CHD group than in the control group 155.7 （124.5-194.5） ng/mL vs. 128.4 （113.0-159.9） ng/mL, P = 0.019. There were no correlation between COMP, Gensini score, Syntax score, severity of coronary stenosis and the number of coronary artery with stenosis 〉 50%. The serum COMP was correlated with age （r = 0.294, P 〈 0.001）, fasting glucose （r = 0.163, P = 0.015）, HbAlc （r = 0.194, P = 0.015） and CACs （r = 0.137, P = 0.037）. Stepwise linear regression analysis showed that COMP level and age were independent predictors of CACs in the CHD patients （fl = 0.402, t = 2.612, P = 0.015; fl = 0.472, t = 3.077, P = 0.005）. Performance of COMP for predicting CHD was shown as area under curve （AUC）： 0.632, 95% CI： 0.549-0.715 and upper tertile CACs was AUC： 0.602, 95% CI： 0.5264）.678 in receiver operating characteristic （ROC） curve analysis. Conclusion Calcification of coronary artery was an independent predictor of serum COMPs.
基金Bengt Ihre Foundation,No.SLS-594-301 and SLS-789091
文摘Serum levels of cartilage oligomeric matrix protein(COMP) has been presented as a biomarker of liver fibrosis in several cross-sectional studies. COMP is also an essential mediator in carcinoma development and has also been associated with hepatocellular carcinoma. We present a prospective analysis of this biomarker in38 patients with chronic hepatitis C who were subject to eradication therapy with direct acting antivirals. We confirm previous studies associating COMP elevation with liver cirrhosis. We also show how viral levels are correlated with COMP at baseline. In our prospective analysis, we report that successful eradication of hepatitis C results in improvement in liver stiffness and laboratory liver function tests at 1 year follow-up. In contrast, median COMP-levels remain unchanged during the study period. We conclude that the biomarker potential of COMP in the prospective evaluation of liver diseases, remains to be elucidated.
文摘Background Pseudoachondroplasia （PSACH） is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein （COMP）.Clinical diagnosis of PSACH is based primarily on family history, physical examination, and radiographic evaluation.There is evidence that decreased serum COMP concentration may serve as a diagnostic marker in PSACH.Here, we investigated the role of this gene and the serum COMP concentration in Chinese patients with PSACH.Methods A family with three patients and a sporadic case were recruited.Genomic and phenotypic data were recorded.The diagnosis of PSACH was made on the base of clinical evaluation.The genomic DNA was extracted from peripheral blood leukocytes.The 8-19 exons and flanking intron-exon boundary sequences of COMP were amplified by polymerase chain reaction （PCR） and screened for mutation by direct DNA sequencing.Serum COMP concentrations of 4 patients and age-compatible control group of 20 unrelated healthy subjects were analyzed on the basis of an ELISA Kit for human cartilage oligomeric matrix protein.Results A deletion （c.1447-1455del） was identified in exon 13 in the sporadic case.The mean serum COMP concentrations of four patients （3.12±2.28） were significantly lower than those of control group （10.86±2.21, P 〈0.05）.There was no overlap in the distribution of serum COMP concentration between PSACH patients and controls.Conclusions Mutations in COMP gene are responsible for the PSACH.Serum COMP concentration may be suggested as an additional diagnostic marker to aid clinical findings in suspected cases of PSACH.
文摘Background Multiple epiphysis dysplasia （MED） is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined.cases, mutations have been identified in the gene encoding cartilage algometric matrix protein （ COMP）. Methods Five patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members. Results We have identified a novel mutation in axon 14 of COMP gene in the family. Conclusions This mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.
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.
