Pub Date : 2023-04-26DOI: 10.1097/CD9.0000000000000087
Lubi Lei, Jingkuo Li, Bin Wang
Objective: This systematic review and meta-analysis aimed to evaluate the efficacy of berberine treatment in improving blood glucose, blood lipids, and blood pressure as well as the associated safety profile. Methods: PubMed, Embase, Cochrane Library, WanFang Data, and the China National Knowledge Infrastructure database were searched from the establishment of the database to December 31, 2021, to identify randomized, double-blind trials that examined the effect of berberine alone or as add-on treatment on blood glucose, blood lipids, and blood pressure with an intervention period of at least 3 months. Two researchers independently screened articles, extracted data, and assessed the quality of each study according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The efficacy outcomes included fasting blood glucose (FPG), 2-hour post-prandial glucose (2hPG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP). The safety outcome was the incidence of the total number of adverse events. Results: A total of 17 articles enrolling 1,485 participants were included in the meta-analysis. The intervention duration ranged from 12 to 24 weeks. Sixteen trials reported results for blood glucose, 14 trials reported results for blood lipids, and 7 reported results for blood pressure. Compared with placebo or baseline treatment, berberine alone or as add-on therapy significantly reduced FPG (by 0.35 mmol/L; 95% confidence interval (CI): 0.13–0.58 mmol/L; P = 0.002; I2 = 89.0%, n = 16), 2hPG (by 1.50 mmol/L; 95% CI: 0.50–2.49 mmol/L, P = 0.003, I2 = 84.1%, n = 4), HbA1c (by 0.45%, 95% CI: 0.24%–0.65%, P < 0.001, I2 = 82.8%, n = 9), TC (by 0.48 mmol/L; 95% CI: 0.36–0.60 mmol/L, P < 0.001, I2 = 72.3%, n = 13), TG (by 0.22 mmol/L; 95% CI: 0.13–0.31 mmol/L, P < 0.001, I2 = 57.1%, n = 14), and LDL-C (by 0.41 mmol/L; 95% CI: 0.34–0.48 mmol/L, P < 0.001, I2 = 35.0%, n = 12). The effect on blood glucose and blood lipids remained consistent when confined to high-quality trials. There is no significant effect of berberine treatment on HDL-C, SBP, and DBP. The incidence of the total number of adverse events was similar between the berberine group and the control group (risk ratio (RR) = 1.00, 95% CI: 0.84–1.19, P = 0.961). Gastrointestinal disorder was the most common adverse event in the berberine group and most adverse events were alleviated or disappeared as the dose was decreased or the intervention time was prolonged. Conclusions: Short-term berberine treatment significantly improved blood glucose and blood lipid profiles without raising safety concerns. A rigorously designed randomized controlled trial could be considered to examine the feasibility of the long-term application of berberine treatment in the prevention of cardiovascular disease.
目的:本系统综述和荟萃分析旨在评估小檗碱治疗在改善血糖、血脂和血压方面的疗效以及相关的安全性。方法:检索PubMed、Embase、Cochrane Library、万方数据和中国国家知识基础设施数据库，检索自数据库建立至2021年12月31日的随机双盲试验，研究黄连素单独或辅助治疗对血糖、血脂和血压的影响，干预期至少为3个月。两名研究人员独立筛选文章，提取数据，并根据系统评价和荟萃分析(PRISMA)指南的首选报告项目评估每个研究的质量。疗效指标包括空腹血糖(FPG)、餐后2小时血糖(2hPG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、收缩压(SBP)和舒张压(DBP)。安全性结局是不良事件总数的发生率。结果:meta分析共纳入17篇文献，1485名受试者。干预时间为12 ~ 24周。16项试验报告了血糖结果，14项试验报告了血脂结果，7项试验报告了血压结果。与安慰剂或基线治疗相比，黄连素单独或附加治疗显著降低FPG (0.35 mmol/L;95%置信区间(CI): 0.13-0.58 mmol/L;P = 0.002;I2 = 89.0%， n = 16)， 2hPG(减1.50 mmol/L;95% CI: 0.50 ~ 2.49 mmol/L, P = 0.003, I2 = 84.1%， n = 4)， HbA1c(下降0.45%，95% CI: 0.24% ~ 0.65%， P < 0.001, I2 = 82.8%， n = 9)， TC(下降0.48 mmol/L;95% CI: 0.36-0.60 mmol/L, P < 0.001, I2 = 72.3%， n = 13)， TG (0.22 mmol/L;95% CI: 0.13-0.31 mmol/L, P < 0.001, I2 = 57.1%， n = 14)， LDL-C (0.41 mmol/L;95% CI: 0.34 ~ 0.48 mmol/L, P < 0.001, I2 = 35.0%， n = 12)。在高质量的试验中，对血糖和血脂的影响保持一致。小檗碱治疗对HDL-C、收缩压和舒张压无显著影响。黄连素组与对照组不良事件总发生率相似(RR = 1.00, 95% CI: 0.84 ~ 1.19, P = 0.961)。胃肠道紊乱是小檗碱组最常见的不良事件，随着剂量的减少或干预时间的延长，大多数不良事件减轻或消失。结论:短期小檗碱治疗可显著改善血糖和血脂，且无安全性问题。可考虑设计严谨的随机对照试验，以检验黄连素长期应用于预防心血管疾病的可行性。
{"title":"Efficacy and Safety Profile of Berberine Treatment in Improving Risk Factors for Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized, Double-blind Trials","authors":"Lubi Lei, Jingkuo Li, Bin Wang","doi":"10.1097/CD9.0000000000000087","DOIUrl":"https://doi.org/10.1097/CD9.0000000000000087","url":null,"abstract":"Objective: This systematic review and meta-analysis aimed to evaluate the efficacy of berberine treatment in improving blood glucose, blood lipids, and blood pressure as well as the associated safety profile. Methods: PubMed, Embase, Cochrane Library, WanFang Data, and the China National Knowledge Infrastructure database were searched from the establishment of the database to December 31, 2021, to identify randomized, double-blind trials that examined the effect of berberine alone or as add-on treatment on blood glucose, blood lipids, and blood pressure with an intervention period of at least 3 months. Two researchers independently screened articles, extracted data, and assessed the quality of each study according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The efficacy outcomes included fasting blood glucose (FPG), 2-hour post-prandial glucose (2hPG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP). The safety outcome was the incidence of the total number of adverse events. Results: A total of 17 articles enrolling 1,485 participants were included in the meta-analysis. The intervention duration ranged from 12 to 24 weeks. Sixteen trials reported results for blood glucose, 14 trials reported results for blood lipids, and 7 reported results for blood pressure. Compared with placebo or baseline treatment, berberine alone or as add-on therapy significantly reduced FPG (by 0.35 mmol/L; 95% confidence interval (CI): 0.13–0.58 mmol/L; P = 0.002; I2 = 89.0%, n = 16), 2hPG (by 1.50 mmol/L; 95% CI: 0.50–2.49 mmol/L, P = 0.003, I2 = 84.1%, n = 4), HbA1c (by 0.45%, 95% CI: 0.24%–0.65%, P < 0.001, I2 = 82.8%, n = 9), TC (by 0.48 mmol/L; 95% CI: 0.36–0.60 mmol/L, P < 0.001, I2 = 72.3%, n = 13), TG (by 0.22 mmol/L; 95% CI: 0.13–0.31 mmol/L, P < 0.001, I2 = 57.1%, n = 14), and LDL-C (by 0.41 mmol/L; 95% CI: 0.34–0.48 mmol/L, P < 0.001, I2 = 35.0%, n = 12). The effect on blood glucose and blood lipids remained consistent when confined to high-quality trials. There is no significant effect of berberine treatment on HDL-C, SBP, and DBP. The incidence of the total number of adverse events was similar between the berberine group and the control group (risk ratio (RR) = 1.00, 95% CI: 0.84–1.19, P = 0.961). Gastrointestinal disorder was the most common adverse event in the berberine group and most adverse events were alleviated or disappeared as the dose was decreased or the intervention time was prolonged. Conclusions: Short-term berberine treatment significantly improved blood glucose and blood lipid profiles without raising safety concerns. A rigorously designed randomized controlled trial could be considered to examine the feasibility of the long-term application of berberine treatment in the prevention of cardiovascular disease.","PeriodicalId":72524,"journal":{"name":"Cardiology discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41447209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-11DOI: 10.1097/CD9.0000000000000088
Xiaona Wang, Ruping Tie, R. Cao, Xu Yang, W. Xiao, L. Sheng, Ping Ye
Objective: The purpose of this study was to determine the relationship between remnant-like particle cholesterol (RLP-C) and major adverse cardiovascular events (MACEs) in patients with different levels of proprotein convertase subtilisin/kexin 9 (PCSK9). Methods: From September 2007 to January 2009, 1,859 subjects in Pingguoyuan communities in Beijing were initially screened. After excluding those with bedridden status, mental illness, severe systemic diseases, and missing data, 1,680 subjects were recruited for follow up. All recruited subjects were followed up from February 2013 to September 2013 (181 subjects were lost to follow-up) and from June 2017 to September 2018 (174 subjects were lost to follow up). Finally, 1,325 subjects were included in the study. General demographic characteristics, lifestyle and behaviors, disease history and use of medication was collected. Levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fast blood glucose, RLP-C, low-density lipoprotein triglycerides and PCSK9 were measured. The levels of RLP-C (low: RLP-C ≤ 157 mg/L; high: RLP-C > 157 mg/L) and PCSK9 (low: PCSK9 ≤ 135.87 μg/L; high: PCSK9 > 135.87 μg/L) were represented using quartiles. Subjects were categorized into 4 groups according to their RLP-C and PCSK9 levels: Q4, high levels of RLP-C with high levels of PCSK9; Q3, high levels of RLP-C with low levels of PCSK9; Q2, low levels of RLP-C with high levels of PCSK9; and Q1, low levels of RLP-C with low levels of PCSK9. The association of RLP-C with MACEs in subjects with different PCSK9 levels was evaluated. Results: After a median follow-up of 9.5 years, 1,325 subjects were included in the study and a total of 191 MACEs had occurred. The incidence of MACEs was higher in the RLP-C > 157 mg/L group than the RLP-C ≤ 157 mg/L group (18.40% vs. 10.42%). Cox proportional hazards regression model analysis showed that increased RLP-C levels were associated with an increased risk of MACEs (hazard ratio: 1.405; 95% confidence interval: 1.005–1.964; P < 0.005). The incidence of MACEs was higher in the high RLP-C/PCSK9 group vs. the low RLP-C/PCSK9 group (20.68% vs. 8.76%). Cox proportional hazards regression model analysis showed that RLP-C was associated with an increased risk of MACEs in subjects with high PCSK9 levels independent of traditional risk factors (hazard ratio: 1.791; 95% confidence interval: 1.168–2.825; P = 0.001), but not in those with low PCSK9 levels. Conclusions: RLP-C was identified as a risk factor for MACEs, particularly in subjects with high PCSK9 levels. Lowering PCSK9 levels may reduce residual risk in subjects with elevated plasma RLP-C levels.
{"title":"Association of Remnant-like Particle Cholesterol with Major Adverse Cardiovascular Events in Subjects with Different Levels of Proprotein Convertase Subtilisin/Kexin 9: A 9.5-year Follow-up Study in a Beijing Community Population","authors":"Xiaona Wang, Ruping Tie, R. Cao, Xu Yang, W. Xiao, L. Sheng, Ping Ye","doi":"10.1097/CD9.0000000000000088","DOIUrl":"https://doi.org/10.1097/CD9.0000000000000088","url":null,"abstract":"Objective: The purpose of this study was to determine the relationship between remnant-like particle cholesterol (RLP-C) and major adverse cardiovascular events (MACEs) in patients with different levels of proprotein convertase subtilisin/kexin 9 (PCSK9). Methods: From September 2007 to January 2009, 1,859 subjects in Pingguoyuan communities in Beijing were initially screened. After excluding those with bedridden status, mental illness, severe systemic diseases, and missing data, 1,680 subjects were recruited for follow up. All recruited subjects were followed up from February 2013 to September 2013 (181 subjects were lost to follow-up) and from June 2017 to September 2018 (174 subjects were lost to follow up). Finally, 1,325 subjects were included in the study. General demographic characteristics, lifestyle and behaviors, disease history and use of medication was collected. Levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fast blood glucose, RLP-C, low-density lipoprotein triglycerides and PCSK9 were measured. The levels of RLP-C (low: RLP-C ≤ 157 mg/L; high: RLP-C > 157 mg/L) and PCSK9 (low: PCSK9 ≤ 135.87 μg/L; high: PCSK9 > 135.87 μg/L) were represented using quartiles. Subjects were categorized into 4 groups according to their RLP-C and PCSK9 levels: Q4, high levels of RLP-C with high levels of PCSK9; Q3, high levels of RLP-C with low levels of PCSK9; Q2, low levels of RLP-C with high levels of PCSK9; and Q1, low levels of RLP-C with low levels of PCSK9. The association of RLP-C with MACEs in subjects with different PCSK9 levels was evaluated. Results: After a median follow-up of 9.5 years, 1,325 subjects were included in the study and a total of 191 MACEs had occurred. The incidence of MACEs was higher in the RLP-C > 157 mg/L group than the RLP-C ≤ 157 mg/L group (18.40% vs. 10.42%). Cox proportional hazards regression model analysis showed that increased RLP-C levels were associated with an increased risk of MACEs (hazard ratio: 1.405; 95% confidence interval: 1.005–1.964; P < 0.005). The incidence of MACEs was higher in the high RLP-C/PCSK9 group vs. the low RLP-C/PCSK9 group (20.68% vs. 8.76%). Cox proportional hazards regression model analysis showed that RLP-C was associated with an increased risk of MACEs in subjects with high PCSK9 levels independent of traditional risk factors (hazard ratio: 1.791; 95% confidence interval: 1.168–2.825; P = 0.001), but not in those with low PCSK9 levels. Conclusions: RLP-C was identified as a risk factor for MACEs, particularly in subjects with high PCSK9 levels. Lowering PCSK9 levels may reduce residual risk in subjects with elevated plasma RLP-C levels.","PeriodicalId":72524,"journal":{"name":"Cardiology discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44250718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-11DOI: 10.1097/CD9.0000000000000085
Jing Li, Yixuan Zhong, J. Bai, Shuohua Chen, Jun Cai, Shouling Wu, Weili Zhang
Objective: Arterial stiffness is an important predictor of cardiovascular disease. Microbial diversity in the gut has been shown to be associated inversely with arterial stiffness in Caucasian populations. However, due to the different profiles of the gut microbiota among ethnicities, the relationship between gut-microbiota dysbiosis and the progression of arterial stiffness merits further investigation. This study aimed to investigate the association between the composition and functional capacity of the gut microbiota and the progression of arterial stiffness. Methods: “Shotgun” metagenomics sequencing were undertaken in 96 individuals from a hypertension-associated gut-microbiota study in the Kailuan cohort, who measured brachial-ankle pulse wave velocity (baPWV) and provided fecal samples between September 2014 and February 2015 at Kailuan General Hospital and 11 affiliated hospitals. The different composition and functional capacity of the gut microbiota were compared between individuals without arterial stiffness (normal arterial stiffness group, baPWV <1,400 cm/s, n = 27) and participants with arterial stiffness (increased arterial stiffness group, baPWV ≥1,400 cm/s, n = 69) at baseline. These participants were followed up prospectively for a mean duration of 2.6 years, and 50 underwent a repeat baPWV measurement. Associations between the gut microbiota and severity and progression of arterial stiffness were assessed using MaAsLin2 software after adjustment for age, sex, and mean arterial blood pressure and correction for multiple testing. Gene “catalogs” were aligned to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to obtain information for potential functional capacities of the gut microbiota. Results: In this study, 14 genera and 50 species of bacteria were identified to be abundant in participants with normal arterial stiffness compared with those with increased arterial stiffness. Of 14 genera, the prevalence of beneficial bacteria of the genera Leadbetterella and Cytophaga was correlated inversely with baPWV (P < 0.05). Analyses of functional capacity revealed gut-microbial dysfunctions in the synthetic processes of “threonine dehydratase” “hypothetical protein” “mannosyl transferase” and “type-IV secretion-system proteins” in individuals suffering from arterial stiffness. During follow-up, bacteria of the proinflammatory genera Escherichia, Shigella, and Ruegeria were enriched in individuals with increased baPWV. Functional analyses showed that 26 KEGG orthologs of gut microbes were associated with an increase in baPWV and involved in “carbohydrate metabolism” “amino acid metabolism” and “protein families related to genetic information processing.” Conclusions: The composition and functional capacity of the microbial community in the gut of people suffering from arterial stiffness differed from those in individuals not suffering from arterial stiffness. Our data provide a new direction for the causality of the host-gu
目的:动脉僵硬度是心血管疾病的重要预测指标。在高加索人群中，肠道微生物多样性已被证明与动脉僵硬度呈负相关。然而，由于不同种族的肠道菌群特征不同，肠道菌群失调与动脉僵硬进展之间的关系值得进一步研究。本研究旨在探讨肠道微生物群的组成和功能能力与动脉硬化进展之间的关系。方法:对来自开滦总医院和11家附属医院的高血压相关肠道微生物群研究的96名个体进行“霰枪”元基因组测序，测量2014年9月至2015年2月期间在开滦总医院和11家附属医院的肱-踝脉波速度(baPWV)并提供粪便样本。比较无动脉僵硬(正常动脉僵硬组，baPWV < 1400 cm/s, n = 27)和动脉僵硬(动脉僵硬增加组，baPWV≥1400 cm/s, n = 69)受试者在基线时肠道微生物群的不同组成和功能能力。对这些参与者进行了平均2.6年的前瞻性随访，其中50人进行了重复的baPWV测量。在调整年龄、性别和平均动脉血压并校正多重测试后，使用MaAsLin2软件评估肠道微生物群与动脉僵硬严重程度和进展之间的关系。基因“目录”与京都基因与基因组百科全书(KEGG)数据库保持一致，以获取肠道微生物群潜在功能的信息。结果:在这项研究中，与动脉僵硬度增高的参与者相比，在动脉僵硬度正常的参与者中鉴定出了14属50种细菌。在14个属中，Leadbetterella和Cytophaga属有益菌的流行率与baPWV呈负相关(P < 0.05)。功能分析显示，患有动脉硬化的个体在“苏氨酸脱水酶”、“假想蛋白”、“甘露糖转移酶”和“iv型分泌系统蛋白”的合成过程中存在肠道微生物功能障碍。在随访期间，促炎属埃希氏菌、志贺氏菌和鲁氏菌在baPWV升高的个体中富集。功能分析显示，肠道微生物的26个KEGG同源物与baPWV的增加有关，并参与“碳水化合物代谢”、“氨基酸代谢”和“与遗传信息处理相关的蛋白质家族”。结论:动脉硬化患者肠道微生物群落的组成和功能能力与非动脉硬化患者不同。我们的数据为宿主肠道微生物群在动脉硬化中的因果关系提供了一个新的方向。
{"title":"Composition and Functional Capacity of Gut Microbes are Associated with Arterial Stiffness: A Prospective Study","authors":"Jing Li, Yixuan Zhong, J. Bai, Shuohua Chen, Jun Cai, Shouling Wu, Weili Zhang","doi":"10.1097/CD9.0000000000000085","DOIUrl":"https://doi.org/10.1097/CD9.0000000000000085","url":null,"abstract":"Objective: Arterial stiffness is an important predictor of cardiovascular disease. Microbial diversity in the gut has been shown to be associated inversely with arterial stiffness in Caucasian populations. However, due to the different profiles of the gut microbiota among ethnicities, the relationship between gut-microbiota dysbiosis and the progression of arterial stiffness merits further investigation. This study aimed to investigate the association between the composition and functional capacity of the gut microbiota and the progression of arterial stiffness. Methods: “Shotgun” metagenomics sequencing were undertaken in 96 individuals from a hypertension-associated gut-microbiota study in the Kailuan cohort, who measured brachial-ankle pulse wave velocity (baPWV) and provided fecal samples between September 2014 and February 2015 at Kailuan General Hospital and 11 affiliated hospitals. The different composition and functional capacity of the gut microbiota were compared between individuals without arterial stiffness (normal arterial stiffness group, baPWV <1,400 cm/s, n = 27) and participants with arterial stiffness (increased arterial stiffness group, baPWV ≥1,400 cm/s, n = 69) at baseline. These participants were followed up prospectively for a mean duration of 2.6 years, and 50 underwent a repeat baPWV measurement. Associations between the gut microbiota and severity and progression of arterial stiffness were assessed using MaAsLin2 software after adjustment for age, sex, and mean arterial blood pressure and correction for multiple testing. Gene “catalogs” were aligned to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to obtain information for potential functional capacities of the gut microbiota. Results: In this study, 14 genera and 50 species of bacteria were identified to be abundant in participants with normal arterial stiffness compared with those with increased arterial stiffness. Of 14 genera, the prevalence of beneficial bacteria of the genera Leadbetterella and Cytophaga was correlated inversely with baPWV (P < 0.05). Analyses of functional capacity revealed gut-microbial dysfunctions in the synthetic processes of “threonine dehydratase” “hypothetical protein” “mannosyl transferase” and “type-IV secretion-system proteins” in individuals suffering from arterial stiffness. During follow-up, bacteria of the proinflammatory genera Escherichia, Shigella, and Ruegeria were enriched in individuals with increased baPWV. Functional analyses showed that 26 KEGG orthologs of gut microbes were associated with an increase in baPWV and involved in “carbohydrate metabolism” “amino acid metabolism” and “protein families related to genetic information processing.” Conclusions: The composition and functional capacity of the microbial community in the gut of people suffering from arterial stiffness differed from those in individuals not suffering from arterial stiffness. Our data provide a new direction for the causality of the host-gu","PeriodicalId":72524,"journal":{"name":"Cardiology discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43373143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01DOI: 10.1097/CD9.0000000000000076
Duofen He, Hongmei Ren, Hongyong Wang, Pedro A Jose, Chunyu Zeng, Tianyang Xia, Jian Yang
Dopamine, via its receptors, plays a vital role in the maintenance of blood pressure by modulating renal sodium transport. However, the role of the D4 dopamine receptor (D4 receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D4 receptor directly inhibits the activity of the Na+-K+-ATPase (NKA) in RPT cells.
Methods: NKA activity, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were measured in RPT cells treated with the D4 receptor agonist PD168077 and/or the D4 receptor antagonist L745870, the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). Total D4 receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs).
Results: Activation of D4 receptors with PD168077, inhibited NKA activity in RPT cells from WKY rats in a concentration- and time-dependent manner. The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D4 receptor antagonist L745870, which by itself had no effect. The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ, which by themselves had no effect on NKA activity, eliminated the inhibitory effect of PD168077 on NKA activity. Activation of D4 receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D4 receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D4 receptors in SHR RPT cells.
Conclusions: Activation of D4 receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs. Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.
多巴胺通过受体调节肾脏钠转运，在维持血压中起着至关重要的作用。然而，D4多巴胺受体(D4受体)在肾近端小管(PRTs)中的作用尚不清楚。本研究旨在验证D4受体的激活直接抑制RPT细胞Na+-K+- atp酶(NKA)活性的假设。方法:分别用D4受体激动剂PD168077和/或D4受体拮抗剂L745870、NO合成酶抑制剂ng -硝基- l -精氨酸甲酯(L-NAME)或可溶性鸟苷环化酶抑制剂1H-[1,2,4]恶二唑-[4,3-a]喹诺沙林-1-one (ODQ)处理RPT细胞，测定NKA活性、一氧化氮(NO)和环鸟苷单磷酸(cGMP)水平。采用免疫印迹法研究了Wistar-Kyoto (WKY)大鼠和自发性高血压大鼠RPT细胞中D4受体的表达及其在质膜中的表达。结果:PD168077激活D4受体后，WKY大鼠RPT细胞中NKA活性呈浓度依赖性和时间依赖性。PD168077对NKA活性的抑制作用被D4受体拮抗剂L745870的加入所阻止，而L745870本身没有作用。NO合酶抑制剂L-NAME和可溶性鸟苷环化酶抑制剂ODQ本身对NKA活性没有影响，消除了PD168077对NKA活性的抑制作用。D4受体的激活也增加了培养液中的NO水平和RPT细胞中的cGMP水平。而在shs RPT细胞中，D4受体对NKA活性的抑制作用不存在，这可能与SHR RPT细胞中D4受体的质膜表达降低有关。结论:D4受体的激活通过NO/cGMP信号通路直接抑制WKY大鼠RPT细胞的NKA活性，而非SHRs。RPT细胞中NKA活性的异常调节可能参与了高血压的发病机制。
{"title":"Effect of D<sub>4</sub> Dopamine Receptor on Na<sup>+</sup>-K<sup>+</sup>-ATPase Activity in Renal Proximal Tubule Cells.","authors":"Duofen He, Hongmei Ren, Hongyong Wang, Pedro A Jose, Chunyu Zeng, Tianyang Xia, Jian Yang","doi":"10.1097/CD9.0000000000000076","DOIUrl":"https://doi.org/10.1097/CD9.0000000000000076","url":null,"abstract":"<p><p>Dopamine, via its receptors, plays a vital role in the maintenance of blood pressure by modulating renal sodium transport. However, the role of the D<sub>4</sub> dopamine receptor (D<sub>4</sub> receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D<sub>4</sub> receptor directly inhibits the activity of the Na<sup>+</sup>-K<sup>+</sup>-ATPase (NKA) in RPT cells.</p><p><strong>Methods: </strong>NKA activity, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were measured in RPT cells treated with the D<sub>4</sub> receptor agonist PD168077 and/or the D<sub>4</sub> receptor antagonist L745870, the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). Total D<sub>4</sub> receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs).</p><p><strong>Results: </strong>Activation of D<sub>4</sub> receptors with PD168077, inhibited NKA activity in RPT cells from WKY rats in a concentration- and time-dependent manner. The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D<sub>4</sub> receptor antagonist L745870, which by itself had no effect. The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ, which by themselves had no effect on NKA activity, eliminated the inhibitory effect of PD168077 on NKA activity. Activation of D<sub>4</sub> receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D<sub>4</sub> receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D<sub>4</sub> receptors in SHR RPT cells.</p><p><strong>Conclusions: </strong>Activation of D<sub>4</sub> receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs. Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.</p>","PeriodicalId":72524,"journal":{"name":"Cardiology discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3c/d0/cd9-3-24.PMC10030170.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-08DOI: 10.1097/CD9.0000000000000081
Jun Dong, Junwu Su, Aijun Liu, Jing Du, Jing Yang, Qiangqiang Li, Bin Li, Ming Yang, Zhijun Wang, Q. Bao
Objective: The size and morphology of the right ventricular outflow tract (RVOT) in patients suffering from long-term pulmonary regurgitation (PR) after native RVOT (NRVOT) reconstruction are important factors affecting the feasibility, safety, and effectiveness of transcatheter pulmonary valve replacement. The purpose of this study was to evaluate the feasibility, safety, and effectiveness of a transthoracic Salus valve (Balance Medical Technology Co., Ltd, Beijing, China) in patients with moderate-to-severe PR after NRVOT reconstruction. Methods: Patients with moderate-to-severe PR after NRVOT reconstruction were selected between June 2021 and November 2021 at Beijing Anzhen Hospital. Demographic data as well as preoperative, intraoperative, and follow-up data were reviewed. Results: Ten patients with moderate-to-severe PR after NRVOT reconstruction underwent physical examination, transthoracic echocardiography, and cardiovascular magnetic resonance imaging. Seven patients were selected for transthoracic Salus valve replacement. Six patients underwent implantation of the Salus valve successfully. One valve migrated and was embolized during recovery of the delivery device; the Salus valve was surgically explanted and sutured to the inner wall of the main pulmonary artery. At a mean follow-up of (5.5 ± 1.1) months, dysfunction or migration of the Salus valve embolism was not observed. Conclusions: This early feasibility study demonstrates the feasibility, safety, and effectiveness of transthoracic implantation of a Salus valve in patients with moderate-to-severe PR after NRVOT reconstruction. The short-term effectiveness is clear, medium and long-term effectiveness requires longer follow-up.
目的:对长期肺返流(PR)患者进行天然右心室流出道(RVOT)重建后右心室流出道(RVOT)的大小和形态是影响经导管肺瓣膜置换术可行性、安全性和有效性的重要因素。本研究的目的是评估经胸主动脉瓣(Balance Medical Technology Co.， Ltd, Beijing, China)在NRVOT重建后中重度PR患者中的可行性、安全性和有效性。方法:选择2021年6月至2021年11月北京安贞医院NRVOT重建术后中重度PR患者。我们回顾了人口统计资料以及术前、术中和随访资料。结果:10例NRVOT重建后中重度PR患者行体格检查、经胸超声心动图及心血管磁共振成像。选择7例患者行经胸上睑瓣置换术。6例患者成功植入上睑瓣。一个瓣膜移位，并在运送装置恢复过程中栓塞;手术切除肺动脉瓣并将其缝合于肺动脉主动脉内壁。在平均(5.5±1.1)个月的随访中，未观察到Salus瓣栓塞的功能障碍或迁移。结论:这项早期可行性研究证明了经胸主动脉瓣植入术治疗NRVOT重建后中重度PR患者的可行性、安全性和有效性。短期疗效明确，中长期疗效需要较长的随访时间。
{"title":"Transthoracic Salus Valve Feasibility Study: Short-Term Outcomes of a Transcatheter Self-Expandable Pulmonary Valve","authors":"Jun Dong, Junwu Su, Aijun Liu, Jing Du, Jing Yang, Qiangqiang Li, Bin Li, Ming Yang, Zhijun Wang, Q. Bao","doi":"10.1097/CD9.0000000000000081","DOIUrl":"https://doi.org/10.1097/CD9.0000000000000081","url":null,"abstract":"Objective: The size and morphology of the right ventricular outflow tract (RVOT) in patients suffering from long-term pulmonary regurgitation (PR) after native RVOT (NRVOT) reconstruction are important factors affecting the feasibility, safety, and effectiveness of transcatheter pulmonary valve replacement. The purpose of this study was to evaluate the feasibility, safety, and effectiveness of a transthoracic Salus valve (Balance Medical Technology Co., Ltd, Beijing, China) in patients with moderate-to-severe PR after NRVOT reconstruction. Methods: Patients with moderate-to-severe PR after NRVOT reconstruction were selected between June 2021 and November 2021 at Beijing Anzhen Hospital. Demographic data as well as preoperative, intraoperative, and follow-up data were reviewed. Results: Ten patients with moderate-to-severe PR after NRVOT reconstruction underwent physical examination, transthoracic echocardiography, and cardiovascular magnetic resonance imaging. Seven patients were selected for transthoracic Salus valve replacement. Six patients underwent implantation of the Salus valve successfully. One valve migrated and was embolized during recovery of the delivery device; the Salus valve was surgically explanted and sutured to the inner wall of the main pulmonary artery. At a mean follow-up of (5.5 ± 1.1) months, dysfunction or migration of the Salus valve embolism was not observed. Conclusions: This early feasibility study demonstrates the feasibility, safety, and effectiveness of transthoracic implantation of a Salus valve in patients with moderate-to-severe PR after NRVOT reconstruction. The short-term effectiveness is clear, medium and long-term effectiveness requires longer follow-up.","PeriodicalId":72524,"journal":{"name":"Cardiology discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46463244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-02DOI: 10.1097/cd9.0000000000000082
Lan Huang
{"title":"Effect of High-Altitude Exposure on the Heart","authors":"Lan Huang","doi":"10.1097/cd9.0000000000000082","DOIUrl":"https://doi.org/10.1097/cd9.0000000000000082","url":null,"abstract":"","PeriodicalId":72524,"journal":{"name":"Cardiology discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41703683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-08DOI: 10.1097/CD9.0000000000000067
Bin Wang, Sicong Ma, Zhiyong Wang, Li Zhang, H. Pei, Yang Zheng, Yue-jing Yang, Zheng Zhang, Xinqun Hu, Ziwen Ren, Feng Zhang, Changqian Wang, Renqiang Yang, Zhiming Yang, Yuexi Wang, G. Fu, Yu Cao, Zuyi Yuan, K. Xu, Xin Zhao, Bo Xu, M. Qiu, Quanmin Jing
Objective: Data comparing the outcomes of MiStent (Micell Technologies, Durham, North Carolina, USA) microcrystalline biodegradable polymer (BP) drug-eluting stent (DES) and those of another post-marketing BP-DES, TIVOLI (EssenTech, Beijing, China) are rare. This study sought to compare the angiographic efficacy and clinical outcomes of the microcrystalline BP sirolimus-eluting stent (SES) system MiStent and those of TIVOLI BP-SES. Methods: The DESSOLVE-C trial was a prospective, single-blinded, multicenter, randomized trial (NCT02448524), which randomly assigned patients with de novo coronary lesions to receive MiStent or TIVOLI BP-SES by a 1:1 ratio. The primary endpoint was a non-inferiority comparison of in-stent late lumen loss (LLL) by quantitative coronary angiography at 9 months. The secondary endpoint was device-related clinical cardiovascular composite events (target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization) and 1-year outcomes. Results: A total of 428 patients (216 patients in the MiStent group and 212 patients in the TIVOLI group) were enrolled and included in an intention-to-treat analysis. MiStent was not only non-inferior but superior to TIVOLI for in-stent LLL at 9 months ((0.23 ± 0.37) mm vs. (0.34 ± 0.48) mm, P for non-inferiority <0.001, P for superiority = 0.02). Although without significant difference, the rate of TLF in MiStent was quantitatively lower than that in TIVOLI (3.70% vs. 6.60%; P = 0.17). Conclusion: Compared with TIVOLI BP-SES, the MiStent system was superior in in-stent LLL at 9 months and had a comparable clinical benefit at 1 year in de novo coronary lesions.
{"title":"A Randomized Controlled Trial of a Biodegradable Polymer, Microcrystalline Sirolimus-Eluting Stent (MiStent) versus Another Biodegradable Polymer Sirolimus-Eluting Stent (TIVOLI): The DESSOLVE-C Trial","authors":"Bin Wang, Sicong Ma, Zhiyong Wang, Li Zhang, H. Pei, Yang Zheng, Yue-jing Yang, Zheng Zhang, Xinqun Hu, Ziwen Ren, Feng Zhang, Changqian Wang, Renqiang Yang, Zhiming Yang, Yuexi Wang, G. Fu, Yu Cao, Zuyi Yuan, K. Xu, Xin Zhao, Bo Xu, M. Qiu, Quanmin Jing","doi":"10.1097/CD9.0000000000000067","DOIUrl":"https://doi.org/10.1097/CD9.0000000000000067","url":null,"abstract":"Objective: Data comparing the outcomes of MiStent (Micell Technologies, Durham, North Carolina, USA) microcrystalline biodegradable polymer (BP) drug-eluting stent (DES) and those of another post-marketing BP-DES, TIVOLI (EssenTech, Beijing, China) are rare. This study sought to compare the angiographic efficacy and clinical outcomes of the microcrystalline BP sirolimus-eluting stent (SES) system MiStent and those of TIVOLI BP-SES. Methods: The DESSOLVE-C trial was a prospective, single-blinded, multicenter, randomized trial (NCT02448524), which randomly assigned patients with de novo coronary lesions to receive MiStent or TIVOLI BP-SES by a 1:1 ratio. The primary endpoint was a non-inferiority comparison of in-stent late lumen loss (LLL) by quantitative coronary angiography at 9 months. The secondary endpoint was device-related clinical cardiovascular composite events (target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization) and 1-year outcomes. Results: A total of 428 patients (216 patients in the MiStent group and 212 patients in the TIVOLI group) were enrolled and included in an intention-to-treat analysis. MiStent was not only non-inferior but superior to TIVOLI for in-stent LLL at 9 months ((0.23 ± 0.37) mm vs. (0.34 ± 0.48) mm, P for non-inferiority <0.001, P for superiority = 0.02). Although without significant difference, the rate of TLF in MiStent was quantitatively lower than that in TIVOLI (3.70% vs. 6.60%; P = 0.17). Conclusion: Compared with TIVOLI BP-SES, the MiStent system was superior in in-stent LLL at 9 months and had a comparable clinical benefit at 1 year in de novo coronary lesions.","PeriodicalId":72524,"journal":{"name":"Cardiology discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44585613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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