Pub Date : 2024-10-01Epub Date: 2024-08-12DOI: 10.1007/s12012-024-09904-y
Yili Shen, Yuxin Hu, Leilei Liu, Jianqin Zhong, Yuxin Zhang, Shenyan Wu, Cheng Chen, Feng Hong
The impact of metal exposure on cardiovascular diseases has become an increasingly concerning topic. To date, few studies have investigated the relationship between the copper-to-zinc ratio and CVD (Cardiovascular disease). This China multi-ethnic cohort study explored the association between the copper-to-zinc ratio and CVD in Chinese adults. The study included a sample size of 9878 people. Logistic regression analysis was used to examine the correlation between urinary copper, urinary zinc, and the copper-to-zinc ratio and CVD prevalence. Restricted cubic spline (RCS) analysis was used to investigate the potential dose-response relationships among copper-to-zinc ratio, urinary copper, urinary zinc, and CVD prevalence. In addition, the least absolute shrinkage and selection operator (LASSO) regression method was used to identify significant risk factors associated with CVD, leading to the development of a nomogram. The predictive performance of the nomogram model for CVD was assessed using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Compared with the copper-to-zinc ratio in Q1, the copper-to-zinc ratio in Q4 was associated with CVD after adjusting for all potential confounders (Model 3) (Q4, odds ratio [OR] 0.608, 95% confidence interval [CI] 0.416-0.889, P = 0.010). After adjusting for all potential confounders (Model 3), urinary copper levels in Q4 were associated with CVD (Q4, odds ratio [OR] 0.627, 95% confidence interval [CI] 0.436-0.902, P = 0.012). No significant difference was found between urinary zinc levels and CVD. The RCS showed a linear dose-response relationship between the copper-to-zinc ratio and CVD (P for overall = 0.01). The nomogram based on the influencing factors examined with LASSO showed good predictive power, and the AUC was 76.3% (95% CI 73.7-78.9%). Our results suggest that there is a significant linear negative correlation between the copper-to-zinc ratio and CVD in Chinese adults and that it has good predictive value for CVD.
{"title":"Association Between the Copper-to-Zinc Ratio and Cardiovascular Disease Among Chinese Adults: A China Multi-ethnic Cohort (CMEC) Study.","authors":"Yili Shen, Yuxin Hu, Leilei Liu, Jianqin Zhong, Yuxin Zhang, Shenyan Wu, Cheng Chen, Feng Hong","doi":"10.1007/s12012-024-09904-y","DOIUrl":"10.1007/s12012-024-09904-y","url":null,"abstract":"<p><p>The impact of metal exposure on cardiovascular diseases has become an increasingly concerning topic. To date, few studies have investigated the relationship between the copper-to-zinc ratio and CVD (Cardiovascular disease). This China multi-ethnic cohort study explored the association between the copper-to-zinc ratio and CVD in Chinese adults. The study included a sample size of 9878 people. Logistic regression analysis was used to examine the correlation between urinary copper, urinary zinc, and the copper-to-zinc ratio and CVD prevalence. Restricted cubic spline (RCS) analysis was used to investigate the potential dose-response relationships among copper-to-zinc ratio, urinary copper, urinary zinc, and CVD prevalence. In addition, the least absolute shrinkage and selection operator (LASSO) regression method was used to identify significant risk factors associated with CVD, leading to the development of a nomogram. The predictive performance of the nomogram model for CVD was assessed using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Compared with the copper-to-zinc ratio in Q1, the copper-to-zinc ratio in Q4 was associated with CVD after adjusting for all potential confounders (Model 3) (Q4, odds ratio [OR] 0.608, 95% confidence interval [CI] 0.416-0.889, P = 0.010). After adjusting for all potential confounders (Model 3), urinary copper levels in Q4 were associated with CVD (Q4, odds ratio [OR] 0.627, 95% confidence interval [CI] 0.436-0.902, P = 0.012). No significant difference was found between urinary zinc levels and CVD. The RCS showed a linear dose-response relationship between the copper-to-zinc ratio and CVD (P for overall = 0.01). The nomogram based on the influencing factors examined with LASSO showed good predictive power, and the AUC was 76.3% (95% CI 73.7-78.9%). Our results suggest that there is a significant linear negative correlation between the copper-to-zinc ratio and CVD in Chinese adults and that it has good predictive value for CVD.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-02DOI: 10.1007/s12012-024-09884-z
Shih-Yi Lee, Shao-Tung Wu, Chen-Xuan Du, Hui-Chun Ku
Oxidative stress causes mitochondrial damage and bioenergetic dysfunction and inhibits adenosine triphosphate production, contributing to the pathogenesis of cardiac diseases. Dipeptidyl peptidase 4 (DPP4) is primarily a membrane-bound extracellular peptidase that cleaves Xaa-Pro or Xaa-Ala dipeptides from the N terminus of polypeptides. DPP4 inhibitors have been used in patients with diabetes and heart failure; however, they have led to inconsistent results. Although the enzymatic properties of DPP4 have been well studied, the substrate-independent functions of DPP4 have not. In the present study, we knocked down DPP4 in cultured cardiomyocytes to exclude the effects of differential alteration in the substrates and metabolites of DPP4 then compared the response between the knocked-down and wild-type cardiomyocytes during exposure to oxidative stress. H2O2 exposure induced DPP4 expression in both types of cardiomyocytes. However, knocking down DPP4 substantially reduced the loss of cell viability by preserving mitochondrial bioenergy, reducing intracellular reactive oxygen species production, and reducing apoptosis-associated protein expression. These findings demonstrate that inhibiting DPP4 improves the body's defense against oxidative stress by enhancing Nrf2 and PGC-1α signaling and increasing superoxide dismutase and catalase activity. Our results indicate that DPP4 mediates the body's response to oxidative stress in individuals with heart disease.
{"title":"Potential Role of Dipeptidyl Peptidase-4 in Regulating Mitochondria and Oxidative Stress in Cardiomyocytes.","authors":"Shih-Yi Lee, Shao-Tung Wu, Chen-Xuan Du, Hui-Chun Ku","doi":"10.1007/s12012-024-09884-z","DOIUrl":"10.1007/s12012-024-09884-z","url":null,"abstract":"<p><p>Oxidative stress causes mitochondrial damage and bioenergetic dysfunction and inhibits adenosine triphosphate production, contributing to the pathogenesis of cardiac diseases. Dipeptidyl peptidase 4 (DPP4) is primarily a membrane-bound extracellular peptidase that cleaves Xaa-Pro or Xaa-Ala dipeptides from the N terminus of polypeptides. DPP4 inhibitors have been used in patients with diabetes and heart failure; however, they have led to inconsistent results. Although the enzymatic properties of DPP4 have been well studied, the substrate-independent functions of DPP4 have not. In the present study, we knocked down DPP4 in cultured cardiomyocytes to exclude the effects of differential alteration in the substrates and metabolites of DPP4 then compared the response between the knocked-down and wild-type cardiomyocytes during exposure to oxidative stress. H<sub>2</sub>O<sub>2</sub> exposure induced DPP4 expression in both types of cardiomyocytes. However, knocking down DPP4 substantially reduced the loss of cell viability by preserving mitochondrial bioenergy, reducing intracellular reactive oxygen species production, and reducing apoptosis-associated protein expression. These findings demonstrate that inhibiting DPP4 improves the body's defense against oxidative stress by enhancing Nrf2 and PGC-1α signaling and increasing superoxide dismutase and catalase activity. Our results indicate that DPP4 mediates the body's response to oxidative stress in individuals with heart disease.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-26DOI: 10.1007/s12012-024-09907-9
Wenjie Zhang, Panpan Wan, Man Zhang, Yanting Chang, Shuli Du, Tianbo Jin, Yuan Wang
One of the causes of coronary heart disease (CHD) is genetic factors. In this study, we explored the relationship between CYP2D7 and TCF20 gene polymorphisms and the risk of CHD in the Han Chinese population. Three single nucleotide polymorphisms (CYP2D7 rs1800754, CYP2D7 rs2743461, and TCF20 rs760648) were selected and genotyped from 490 cases and 480 controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between CYP2D7 and TCF20 polymorphisms and the risk of CHD. The association between clinical indicators and polymorphisms was analyzed using one-way ANOVA and Tukey's HSD. The SNP-SNP interactions were obtained by performing multifactor dimensionality reduction (MDR). CYP2D7 rs1800754 and rs2743461 were closely associated with increased risk of CHD (alleles: p = 0.014, p = 0.031). Stratified analysis showed that CYP2D7 rs1800754 and rs2743461 were associated with an increased risk of CHD in men, age > 60 years, BMI ≥ 24, and smoking. Rs1800754 is also associated with an increased risk of CHD associated with alcohol consumption. In addition, TCF20 rs760648 was associated with a reduced risk of CHD in patients aged ≤ 60 years and with CALs. A significant association was found between CYP2D7 rs1800754 and rs2743461 genotypes and levels of UREA, Cr, and LDL-C; TCF20 rs760648 genotypes and levels of RBC. The MDR analysis showed that the three-locus interaction model was the best in the multi-locus model. In conclusion, CYP2D7 rs1800754 and rs2743461 polymorphisms were associated with CHD risk.
{"title":"Association Between CYP2D7 and TCF20 Polymorphisms and Coronary Heart Disease.","authors":"Wenjie Zhang, Panpan Wan, Man Zhang, Yanting Chang, Shuli Du, Tianbo Jin, Yuan Wang","doi":"10.1007/s12012-024-09907-9","DOIUrl":"10.1007/s12012-024-09907-9","url":null,"abstract":"<p><p>One of the causes of coronary heart disease (CHD) is genetic factors. In this study, we explored the relationship between CYP2D7 and TCF20 gene polymorphisms and the risk of CHD in the Han Chinese population. Three single nucleotide polymorphisms (CYP2D7 rs1800754, CYP2D7 rs2743461, and TCF20 rs760648) were selected and genotyped from 490 cases and 480 controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between CYP2D7 and TCF20 polymorphisms and the risk of CHD. The association between clinical indicators and polymorphisms was analyzed using one-way ANOVA and Tukey's HSD. The SNP-SNP interactions were obtained by performing multifactor dimensionality reduction (MDR). CYP2D7 rs1800754 and rs2743461 were closely associated with increased risk of CHD (alleles: p = 0.014, p = 0.031). Stratified analysis showed that CYP2D7 rs1800754 and rs2743461 were associated with an increased risk of CHD in men, age > 60 years, BMI ≥ 24, and smoking. Rs1800754 is also associated with an increased risk of CHD associated with alcohol consumption. In addition, TCF20 rs760648 was associated with a reduced risk of CHD in patients aged ≤ 60 years and with CALs. A significant association was found between CYP2D7 rs1800754 and rs2743461 genotypes and levels of UREA, Cr, and LDL-C; TCF20 rs760648 genotypes and levels of RBC. The MDR analysis showed that the three-locus interaction model was the best in the multi-locus model. In conclusion, CYP2D7 rs1800754 and rs2743461 polymorphisms were associated with CHD risk.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-08-13DOI: 10.1007/s12012-024-09912-y
Xiao-Min Luo, Min Tang, Xiao-Hui Wei, Xiaofang Tang, Yong-De Peng
Previous studies have found a possible association between nickel and metabolic syndrome (MetS), but with conflicting results. No studies have determined whether nickel exposure increases the prevalence of MetS in the general U.S. population. Therefore, we used data from the National Health and Nutrition Examination Survey (NHANES) to assess the association between urinary nickel and MetS. Since urinary nickel levels were presented as a skewed distribution, they were normalized using a logarithmic transformation. Weighted multivariate logistic models, restricted cubic spline, threshold effect analysis, and subgroup analyses were used to examine the association between urinary nickel concentration and the risk of MetS and its components. Based on data from 1577 participants, individuals in the second, third, and fourth quartiles of urinary nickel had an adjusted OR for MetS of 1.42 (95% CI: 0.88, 2.28), 2.00 (95% CI: 1.22, 3.28), and 1.68 (95% CI: 1.05, 2.70), respectively, representing an inverted "L"-shaped nonlinear dose-response relationship with an inflection point at 0.2141 ng/L. Patients over the age of 40, males, less educated, and smokers are more susceptible to nickel exposure. In addition, there were significant associations between nickel and most components of the MetS, with the strongest to weakest correlations being high fasting glucose, reduced high-density lipoprotein, abdominal obesity, and elevated blood pressure; however, there was no significant correlation between nickel and hyperlipidemia. In conclusion, environmental nickel exposure increases the prevalence of MetS in U.S. adults, particularly in males over 40 years of age, those with less education, and smokers.
{"title":"Association Between Nickel Exposure and Metabolic Syndrome: Data from NHANES 2017-2018.","authors":"Xiao-Min Luo, Min Tang, Xiao-Hui Wei, Xiaofang Tang, Yong-De Peng","doi":"10.1007/s12012-024-09912-y","DOIUrl":"10.1007/s12012-024-09912-y","url":null,"abstract":"<p><p>Previous studies have found a possible association between nickel and metabolic syndrome (MetS), but with conflicting results. No studies have determined whether nickel exposure increases the prevalence of MetS in the general U.S. population. Therefore, we used data from the National Health and Nutrition Examination Survey (NHANES) to assess the association between urinary nickel and MetS. Since urinary nickel levels were presented as a skewed distribution, they were normalized using a logarithmic transformation. Weighted multivariate logistic models, restricted cubic spline, threshold effect analysis, and subgroup analyses were used to examine the association between urinary nickel concentration and the risk of MetS and its components. Based on data from 1577 participants, individuals in the second, third, and fourth quartiles of urinary nickel had an adjusted OR for MetS of 1.42 (95% CI: 0.88, 2.28), 2.00 (95% CI: 1.22, 3.28), and 1.68 (95% CI: 1.05, 2.70), respectively, representing an inverted \"L\"-shaped nonlinear dose-response relationship with an inflection point at 0.2141 ng/L. Patients over the age of 40, males, less educated, and smokers are more susceptible to nickel exposure. In addition, there were significant associations between nickel and most components of the MetS, with the strongest to weakest correlations being high fasting glucose, reduced high-density lipoprotein, abdominal obesity, and elevated blood pressure; however, there was no significant correlation between nickel and hyperlipidemia. In conclusion, environmental nickel exposure increases the prevalence of MetS in U.S. adults, particularly in males over 40 years of age, those with less education, and smokers.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The studies regarding prevalence, outcomes, and predictors of prolonged corrected QT (QTc) among COVID-19 patients not on QTc-prolonging medication are not available in the literature. In this retrospective cohort study, the QTc of 295 hospital-admitted COVID-19 patients was analyzed and its association with in-hospital mortality was determined. The QTc was prolonged in 14.6% (43/295) of the study population. Prolonged QTc was seen in patients with older age (P = 0.018), coronary artery disease (P = 0.001), congestive heart failure (P = 0.042), elevated N-terminal-pro-B-type natriuretic peptide (NT-ProBNP) (P < 0.0001), and on remdesivir (P = 0.046). No episode of torsades de pointes arrhythmia or any arrhythmic death was observed among patients with prolonged QTc. The mortality was significantly high in patients with prolonged QTc (P = 0.003). The multivariate logistic regression analysis showed coronary artery disease (odds ratio (OR): 4.153, 95% CI 1.37-14.86; P = 0.013), and NT-ProBNP (ng/L) (OR: 1.000, 95% CI 1.000-1.000; P = 0.007) as predictors of prolonged QTc. The prolonged QTc was associated with the worst in-hospital survival (p by log-rank 0.001). A significant independent association was observed between prolonged QTc and in-hospital mortality in multivariate cox-regression analysis (adjusted hazard ratio: 3.861; (95% CI 1.719-6.523), P < 0.0001). QTc was found to be a marker of underlying comorbidities among COVID-19 patients. Prolonged QTc in hospitalized COVID-19 patients was independently associated with in-hospital mortality.
有关未服用QTc延长药物的COVID-19患者中校正QT(QTc)延长的发生率、结果和预测因素的研究在文献中并不多见。在这项回顾性队列研究中,对 295 名入院的 COVID-19 患者的 QTc 进行了分析,并确定了其与院内死亡率的关系。研究人群中有 14.6%(43/295)的患者 QTc 延长。QTc延长见于年龄较大(P = 0.018)、患有冠状动脉疾病(P = 0.001)、充血性心力衰竭(P = 0.042)、N-末端前 B 型钠尿肽(NT-ProBNP)升高(P = 0.001)、N-末端前 B 型钠尿肽(NT-ProBNP)升高(P = 0.042)和N-末端前 B 型钠尿肽(NT-ProBNP)升高(P = 0.018)的患者。
{"title":"Prevalence, Outcomes, and Predictors of Prolonged Corrected QT Interval in Hydroxychloroquine-Naïve Hospitalized COVID-19 Patients.","authors":"Praveen Gupta, Anunay Gupta, Kapil Gupta, Sandeep Bansal, Monica Sharma, Ira Balakrishnan","doi":"10.1007/s12012-024-09886-x","DOIUrl":"10.1007/s12012-024-09886-x","url":null,"abstract":"<p><p>The studies regarding prevalence, outcomes, and predictors of prolonged corrected QT (QTc) among COVID-19 patients not on QTc-prolonging medication are not available in the literature. In this retrospective cohort study, the QTc of 295 hospital-admitted COVID-19 patients was analyzed and its association with in-hospital mortality was determined. The QTc was prolonged in 14.6% (43/295) of the study population. Prolonged QTc was seen in patients with older age (P = 0.018), coronary artery disease (P = 0.001), congestive heart failure (P = 0.042), elevated N-terminal-pro-B-type natriuretic peptide (NT-ProBNP) (P < 0.0001), and on remdesivir (P = 0.046). No episode of torsades de pointes arrhythmia or any arrhythmic death was observed among patients with prolonged QTc. The mortality was significantly high in patients with prolonged QTc (P = 0.003). The multivariate logistic regression analysis showed coronary artery disease (odds ratio (OR): 4.153, 95% CI 1.37-14.86; P = 0.013), and NT-ProBNP (ng/L) (OR: 1.000, 95% CI 1.000-1.000; P = 0.007) as predictors of prolonged QTc. The prolonged QTc was associated with the worst in-hospital survival (p by log-rank 0.001). A significant independent association was observed between prolonged QTc and in-hospital mortality in multivariate cox-regression analysis (adjusted hazard ratio: 3.861; (95% CI 1.719-6.523), P < 0.0001). QTc was found to be a marker of underlying comorbidities among COVID-19 patients. Prolonged QTc in hospitalized COVID-19 patients was independently associated with in-hospital mortality.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-08DOI: 10.1007/s12012-024-09889-8
Xiaobiao Cao, Jun Yang, Lujun He, Cangcang Liu
Atherosclerosis (AS) is an inflammatory disease with multiple causes. Multiple circular RNAs (circRNAs) are known to be involved in the pathogenesis of AS. To explore the function and mechanism of circ_0005699 in oxidative low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) injury. Ox-LDL treatment restrained HUVECs viability, cell proliferation, and angiogenesis ability, and accelerated HUVECs apoptosis, inflammatory response, and oxidative stress. Circ_0005699 was up-regulated in the serum samples of AS patients and ox-LDL-induced HUVECs. Interference of circ_0005699 effectively rescued ox-LDL-induced injury in HUVECs. Additionally, miR-384 could bind to circ_0005699, and miR-384 depletion inverted the effects of circ_0005699 deficiency on ox-LDL-mediated HUVEC injury. Moreover, ASPH was a direct target of miR-384, and the enforced expression of ASPH overturned miR-384-induced effects on ox-LDL-induced HUVECs. Importantly, circ_0005699 regulated ASPH expression via sponging miR-384. Interference of circ_0005699 protected against ox-LDL-induced injury in HUVECs at least partly by regulating ASPH expression via acting as a miR-384 sponge.
{"title":"Circ_0005699 Expedites ox-LDL-Triggered Endothelial Cell Injury via Targeting miR-384/ASPH Axis.","authors":"Xiaobiao Cao, Jun Yang, Lujun He, Cangcang Liu","doi":"10.1007/s12012-024-09889-8","DOIUrl":"10.1007/s12012-024-09889-8","url":null,"abstract":"<p><p>Atherosclerosis (AS) is an inflammatory disease with multiple causes. Multiple circular RNAs (circRNAs) are known to be involved in the pathogenesis of AS. To explore the function and mechanism of circ_0005699 in oxidative low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) injury. Ox-LDL treatment restrained HUVECs viability, cell proliferation, and angiogenesis ability, and accelerated HUVECs apoptosis, inflammatory response, and oxidative stress. Circ_0005699 was up-regulated in the serum samples of AS patients and ox-LDL-induced HUVECs. Interference of circ_0005699 effectively rescued ox-LDL-induced injury in HUVECs. Additionally, miR-384 could bind to circ_0005699, and miR-384 depletion inverted the effects of circ_0005699 deficiency on ox-LDL-mediated HUVEC injury. Moreover, ASPH was a direct target of miR-384, and the enforced expression of ASPH overturned miR-384-induced effects on ox-LDL-induced HUVECs. Importantly, circ_0005699 regulated ASPH expression via sponging miR-384. Interference of circ_0005699 protected against ox-LDL-induced injury in HUVECs at least partly by regulating ASPH expression via acting as a miR-384 sponge.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-07-26DOI: 10.1007/s12012-024-09900-2
Yanping Li, Yi Zhou, Haifeng Pei, De Li
Reperfusion after myocardial infarction (MI) can lead to myocardial ischemia/reperfusion (I/R) damage. The transcription factor (TF) broad-complex, tramtrack, and bric-a-brac (BTB) and cap'n'collar (CNC) homology 1 (BACH1) is implicated in the injury. However, the downstream mechanisms of BACH1 in affecting myocardial hypoxia/reoxygenation (H/R) damage are still fully understood. AC16 cells were stimulated with H/R conditions to model cardiomyocytes under H/R. mRNA analysis was performed by quantitative real-time PCR. Protein levels were gauged by immunoblot analysis. The effect of BACH1/cyclin-dependent kinase inhibitor 3 (CDKN3) on H/R-evoked injury was assessed by measuring cell viability via Cell Counting Kit-8 (CCK-8), apoptosis (flow cytometry and caspase 3 activity), ferroptosis via Fe2+, glutathione (GSH), reactive oxygen species (ROS) and malondialdehyde (MDA) markers and inflammation cytokines interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNF-α). The BACH1/CDKN3 relationship was examined by chromatin immunoprecipitation (ChIP) experiment and luciferase assay. BACH1 was increased in MI serum and H/R-stimulated AC16 cardiomyocytes. Functionally, disruption of BACH1 mitigated H/R-evoked in vitro apoptosis, ferroptosis and inflammation of AC16 cardiomyocytes. Mechanistically, BACH1 activated CDKN3 transcription and enhanced CDKN3 protein expression in AC16 cardiomyocytes. Our rescue experiments validated that BACH1 disruption attenuated H/R-evoked AC16 cardiomyocyte apoptosis, ferroptosis and inflammation by downregulating CDKN3. Additionally, BACH1 disruption could activate the adenosine monophosphate-activated protein kinase (AMPK) signaling by downregulating CDKN3 in H/R-stimulated AC16 cardiomyocytes. Our study demonstrates that BACH1 activates CDKN3 transcription to induce H/R-evoked damage of AC16 cardiomyocytes partially via AMPK signaling.
{"title":"Disruption of BACH1 Protects AC16 Cardiomyocytes Against Hypoxia/Reoxygenation-Evoked Injury by Diminishing CDKN3 Transcription.","authors":"Yanping Li, Yi Zhou, Haifeng Pei, De Li","doi":"10.1007/s12012-024-09900-2","DOIUrl":"10.1007/s12012-024-09900-2","url":null,"abstract":"<p><p>Reperfusion after myocardial infarction (MI) can lead to myocardial ischemia/reperfusion (I/R) damage. The transcription factor (TF) broad-complex, tramtrack, and bric-a-brac (BTB) and cap'n'collar (CNC) homology 1 (BACH1) is implicated in the injury. However, the downstream mechanisms of BACH1 in affecting myocardial hypoxia/reoxygenation (H/R) damage are still fully understood. AC16 cells were stimulated with H/R conditions to model cardiomyocytes under H/R. mRNA analysis was performed by quantitative real-time PCR. Protein levels were gauged by immunoblot analysis. The effect of BACH1/cyclin-dependent kinase inhibitor 3 (CDKN3) on H/R-evoked injury was assessed by measuring cell viability via Cell Counting Kit-8 (CCK-8), apoptosis (flow cytometry and caspase 3 activity), ferroptosis via Fe<sup>2+</sup>, glutathione (GSH), reactive oxygen species (ROS) and malondialdehyde (MDA) markers and inflammation cytokines interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNF-α). The BACH1/CDKN3 relationship was examined by chromatin immunoprecipitation (ChIP) experiment and luciferase assay. BACH1 was increased in MI serum and H/R-stimulated AC16 cardiomyocytes. Functionally, disruption of BACH1 mitigated H/R-evoked in vitro apoptosis, ferroptosis and inflammation of AC16 cardiomyocytes. Mechanistically, BACH1 activated CDKN3 transcription and enhanced CDKN3 protein expression in AC16 cardiomyocytes. Our rescue experiments validated that BACH1 disruption attenuated H/R-evoked AC16 cardiomyocyte apoptosis, ferroptosis and inflammation by downregulating CDKN3. Additionally, BACH1 disruption could activate the adenosine monophosphate-activated protein kinase (AMPK) signaling by downregulating CDKN3 in H/R-stimulated AC16 cardiomyocytes. Our study demonstrates that BACH1 activates CDKN3 transcription to induce H/R-evoked damage of AC16 cardiomyocytes partially via AMPK signaling.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The present study focused on exploring the clinical value and molecular mechanism of LncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in sepsis and sepsis-induced myocardial dysfunction (SIMD). 122 sepsis patients and 90 healthy were included. Sepsis patients were categorized into SIMD and non-MD. The expression levels of MCM3AP-AS1 and miRNA were examined using RT-qPCR. Diagnostic value of MCM3AP-AS1 in sepsis assessed by ROC curves. Logistic regression to explore risk factors influencing the occurrence of SIMD. Cardiomyocytes were induced by LPS to construct cell models in vitro. CCK-8, flow cytometry, and ELISA to analyze cell viability, apoptosis, and inflammation levels. Serum MCM3AP-AS1 was upregulated in patients with sepsis. The sensitivity and specificity of MCM3AP-AS1 were 75.41% and 93.33%, for recognizing sepsis from healthy controls. Additionally, elevated MCM3AP-AS1 is a risk factor for SIMD and can predict SIMD development. Compared with the LPS-induced cardiomyocytes, inhibition of MCM3AP-AS1 significantly attenuated LPS-induced apoptosis and inflammation; however, this attenuation was partially reversed by lowered miR-28-5p, but this reversal was partially eliminated by CASP2. MCM3AP-AS1 may be a novel diagnostic biomarker for sepsis and can predict the development of SIMD. MCM3AP-AS1 probably participated in SIMD progression by regulating cardiomyocyte inflammation and apoptosis through the target miR-28-5p/CASP2 axis.
{"title":"Diagnostic and Predictive Value of LncRNA MCM3AP-AS1 in Sepsis and Its Regulatory Role in Sepsis-Induced Myocardial Dysfunction.","authors":"Yunwei Wei, Cui Bai, Shuying Xu, Mingli Cui, Ruixia Wang, Meizhen Wu","doi":"10.1007/s12012-024-09903-z","DOIUrl":"10.1007/s12012-024-09903-z","url":null,"abstract":"<p><p>The present study focused on exploring the clinical value and molecular mechanism of LncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in sepsis and sepsis-induced myocardial dysfunction (SIMD). 122 sepsis patients and 90 healthy were included. Sepsis patients were categorized into SIMD and non-MD. The expression levels of MCM3AP-AS1 and miRNA were examined using RT-qPCR. Diagnostic value of MCM3AP-AS1 in sepsis assessed by ROC curves. Logistic regression to explore risk factors influencing the occurrence of SIMD. Cardiomyocytes were induced by LPS to construct cell models in vitro. CCK-8, flow cytometry, and ELISA to analyze cell viability, apoptosis, and inflammation levels. Serum MCM3AP-AS1 was upregulated in patients with sepsis. The sensitivity and specificity of MCM3AP-AS1 were 75.41% and 93.33%, for recognizing sepsis from healthy controls. Additionally, elevated MCM3AP-AS1 is a risk factor for SIMD and can predict SIMD development. Compared with the LPS-induced cardiomyocytes, inhibition of MCM3AP-AS1 significantly attenuated LPS-induced apoptosis and inflammation; however, this attenuation was partially reversed by lowered miR-28-5p, but this reversal was partially eliminated by CASP2. MCM3AP-AS1 may be a novel diagnostic biomarker for sepsis and can predict the development of SIMD. MCM3AP-AS1 probably participated in SIMD progression by regulating cardiomyocyte inflammation and apoptosis through the target miR-28-5p/CASP2 axis.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1007/s12012-024-09927-5
Seyed Hadi Hosseini, Maryam Nazarian, Shahnaz Rajabi, Amir Masoud Jafari-Nozad, Behzad Mesbahzadeh, Saeed Samargahndian, Tahereh Farkhondeh
Arsenic trioxide (ATO) is a potent and highly effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, the clinical use of ATO is hampered by different cardiopathologic outcomes, such as arrhythmia and heart failure. Berberine has several beneficial effects because of its antioxidant activity; however, the potential cardioprotective function of this alkaloid against arsenic-induced cardiac toxicity has not been fully investigated. In this study, we evaluated the effect of ATO in rat heart tissue and the effect of berberine nanoparticles (NB) on cardiac enzyme levels, oxidative stress (OS) indices, and histopathological changes in heart tissue. Thirty Wistar rats were randomly allocated into five groups (n = 6): (1) Control animals that received 0.5 cc saline via gavage, (2) ATO group (4 mg/kg), (3) ATO + NB (2.5 mg/kg), (4) ATO + NB (5 mg/kg), and (5) ATO + NB (10 mg/kg) groups. Treatments were administered intraperitoneally for 45 days. Cardiac enzymes and OS biomarkers in heart tissue were measured. Histopathological examination of the heart tissue was also conducted at the end of the study. ATO injection significantly increased cardiac enzyme levels and OS biomarkers in rat's heart tissue. It also changed the histological features of the heart. NB administration significantly decreased the serum and tissue levels of cardiac enzyme and OS biomarkers in ATO-exposed animals (p < 0.05) and improved myocardial structural damage. NB, potent antioxidant, can reduce the unfavorable effects of ATO in rat heart tissue by balancing OS markers.
三氧化二砷(ATO)是治疗急性早幼粒细胞白血病的强效化疗药物。然而,三氧化二砷在临床上的应用却受到心律失常和心力衰竭等不同心脏病理结果的阻碍。小檗碱具有抗氧化活性,因此有多种有益的作用;然而,这种生物碱对砷引起的心脏毒性的潜在心脏保护功能尚未得到充分研究。在这项研究中,我们评估了砷化钾对大鼠心脏组织的影响,以及小檗碱纳米颗粒(NB)对心脏酶水平、氧化应激(OS)指数和心脏组织病理变化的影响。将 30 只 Wistar 大鼠随机分为 5 组(n = 6):(1) 对照组,灌胃 0.5 cc 生理盐水;(2) ATO 组(4 mg/kg);(3) ATO + NB 组(2.5 mg/kg);(4) ATO + NB 组(5 mg/kg);(5) ATO + NB 组(10 mg/kg)。腹腔注射治疗 45 天。测量心脏组织中的心肌酶和操作系统生物标志物。研究结束时还对心脏组织进行了组织病理学检查。注射 ATO 后,大鼠心脏组织中的心肌酶水平和 OS 生物标志物明显增加。它还改变了心脏的组织学特征。注射 NB 能明显降低 ATO 暴露动物血清和组织中的心肌酶和操作系统生物标志物水平(p < 0.05),并改善心肌结构损伤。NB是一种强效抗氧化剂,可通过平衡OS标志物减轻ATO对大鼠心脏组织的不利影响。
{"title":"Protective Effect of Berberine Nanoparticles Against Cardiotoxic Effects of Arsenic Trioxide.","authors":"Seyed Hadi Hosseini, Maryam Nazarian, Shahnaz Rajabi, Amir Masoud Jafari-Nozad, Behzad Mesbahzadeh, Saeed Samargahndian, Tahereh Farkhondeh","doi":"10.1007/s12012-024-09927-5","DOIUrl":"https://doi.org/10.1007/s12012-024-09927-5","url":null,"abstract":"<p><p>Arsenic trioxide (ATO) is a potent and highly effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, the clinical use of ATO is hampered by different cardiopathologic outcomes, such as arrhythmia and heart failure. Berberine has several beneficial effects because of its antioxidant activity; however, the potential cardioprotective function of this alkaloid against arsenic-induced cardiac toxicity has not been fully investigated. In this study, we evaluated the effect of ATO in rat heart tissue and the effect of berberine nanoparticles (NB) on cardiac enzyme levels, oxidative stress (OS) indices, and histopathological changes in heart tissue. Thirty Wistar rats were randomly allocated into five groups (n = 6): (1) Control animals that received 0.5 cc saline via gavage, (2) ATO group (4 mg/kg), (3) ATO + NB (2.5 mg/kg), (4) ATO + NB (5 mg/kg), and (5) ATO + NB (10 mg/kg) groups. Treatments were administered intraperitoneally for 45 days. Cardiac enzymes and OS biomarkers in heart tissue were measured. Histopathological examination of the heart tissue was also conducted at the end of the study. ATO injection significantly increased cardiac enzyme levels and OS biomarkers in rat's heart tissue. It also changed the histological features of the heart. NB administration significantly decreased the serum and tissue levels of cardiac enzyme and OS biomarkers in ATO-exposed animals (p < 0.05) and improved myocardial structural damage. NB, potent antioxidant, can reduce the unfavorable effects of ATO in rat heart tissue by balancing OS markers.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-22DOI: 10.1007/s12012-024-09921-x
Mohammad Mahdi Dabbaghi, Hesan Soleimani Roudi, Rozhan Safaei, Vafa Baradaran Rahimi, Mohammad Reza Fadaei, Vahid Reza Askari
Tanshinone, a natural compound found in the roots of Salvia miltiorrhiza, has been shown to possess various pharmacological properties, including anti-inflammatory, antioxidant, and cardiovascular protective effects. This article aims to review the literature on the cardiovascular protective effects of tanshinone and its underlying mechanisms. Tanshinone has been demonstrated to improve cardiac function, reduce oxidative stress, and inhibit inflammation in various animal models of cardiovascular diseases. Additionally, it has been shown to regulate multiple signaling pathways involved in the pathogenesis of cardiovascular diseases, such as the PI3K/AKT, MAPK, and NF-κB pathways. Clinical studies have also suggested that tanshinone may have therapeutic potential for treating cardiovascular diseases. In conclusion, tanshinone has emerged as a promising natural compound with significant cardiovascular protective effects, and further research is warranted to explore its potential clinical applications.
{"title":"Unveiling the Mechanism of Protective Effects of Tanshinone as a New Fighter Against Cardiovascular Diseases: A Systematic Review.","authors":"Mohammad Mahdi Dabbaghi, Hesan Soleimani Roudi, Rozhan Safaei, Vafa Baradaran Rahimi, Mohammad Reza Fadaei, Vahid Reza Askari","doi":"10.1007/s12012-024-09921-x","DOIUrl":"https://doi.org/10.1007/s12012-024-09921-x","url":null,"abstract":"<p><p>Tanshinone, a natural compound found in the roots of Salvia miltiorrhiza, has been shown to possess various pharmacological properties, including anti-inflammatory, antioxidant, and cardiovascular protective effects. This article aims to review the literature on the cardiovascular protective effects of tanshinone and its underlying mechanisms. Tanshinone has been demonstrated to improve cardiac function, reduce oxidative stress, and inhibit inflammation in various animal models of cardiovascular diseases. Additionally, it has been shown to regulate multiple signaling pathways involved in the pathogenesis of cardiovascular diseases, such as the PI<sub>3</sub>K/AKT, MAPK, and NF-κB pathways. Clinical studies have also suggested that tanshinone may have therapeutic potential for treating cardiovascular diseases. In conclusion, tanshinone has emerged as a promising natural compound with significant cardiovascular protective effects, and further research is warranted to explore its potential clinical applications.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}