Cardiovascular Diabetology最新文献

{"title":"BMI variability and cardiovascular outcomes within clinical trial and real-world environments in type 2 diabetes: an IMI2 SOPHIA study.","authors":"Robert J Massey, Yu Chen, Marina Panova-Noeva, Michaela Mattheus, Moneeza K Siddiqui, Nanette C Schloot, Antonio Ceriello, Ewan R Pearson, Adem Y Dawed","doi":"10.1186/s12933-024-02299-8","DOIUrl":"10.1186/s12933-024-02299-8","url":null,"abstract":"<p><strong>Background: </strong>BMI variability has been associated with increased cardiovascular disease risk in individuals with type 2 diabetes, however comparison between clinical studies and real-world observational evidence has been lacking. Furthermore, it is not known whether BMI variability has an effect independent of HbA1c variability.</p><p><strong>Methods: </strong>We investigated the association between BMI variability and 3P-MACE risk in the Harmony Outcomes trial (n = 9198), and further analysed placebo arms of REWIND (n = 4440) and EMPA-REG OUTCOME (n = 2333) trials, followed by real-world data from the Tayside Bioresource (n = 6980) using Cox regression modelling. BMI variability was determined using average successive variability (ASV), with first major adverse cardiovascular event of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death (3P-MACE) as the primary outcome.</p><p><strong>Results: </strong>After adjusting for cardiovascular risk factors, a + 1 SD increase in BMI variability was associated with increased 3P-MACE risk in Harmony Outcomes (HR 1.12, 95% CI 1.08-1.17, P < 0.001). The most variable quartile of participants experienced an 87% higher risk of 3P-MACE (P < 0.001) relative to the least variable. Similar associations were found in REWIND and Tayside Bioresource. Further analyses in the EMPA-REG OUTCOME trial did not replicate this association. BMI variability's impact on 3P-MACE risk was independent of HbA1c variability.</p><p><strong>Conclusions: </strong>In individuals with type 2 diabetes, increased BMI variability was found to be an independent risk factor for 3P-MACE across cardiovascular outcome trials and real-world datasets. Future research should attempt to establish a causal relationship between BMI variability and cardiovascular outcomes.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of atherogenic index of plasma with cardiovascular disease mortality and all-cause mortality in the general US adult population: results from NHANES 2005-2018.","authors":"Minghui Qin, Bo Chen","doi":"10.1186/s12933-024-02359-z","DOIUrl":"10.1186/s12933-024-02359-z","url":null,"abstract":"<p><strong>Background: </strong>The atherogenic index of plasma (AIP) is a critical metric for predicting cardiovascular outcomes. However, its associations with cardiovascular disease mortality (CVM) and all-cause mortality (ACM) remain unclear. This study aims to elucidate the relationship between baseline AIP levels and CVM and ACM among a broad cohort of US adults.</p><p><strong>Methods: </strong>Utilizing data from the National Health and Nutrition Examination Survey (2005-2018), we analyzed 18,133 adults aged ≥ 18. Baseline triglycerides and high-density lipoprotein cholesterol levels were measured to calculate the AIP. Mortality outcomes were determined through linkage with the National Death Index database, with follow-up through December 31, 2019. Multivariable Cox proportional hazard models examined the associations between baseline AIP and mortality risks. Additionally, restricted cubic splines were utilized to investigate potential non-linear relationships, with subgroup analyses conducted across strata defined by age, gender, body mass index, diabetes, hypertension, and metabolic syndrome to assess variability in these associations.</p><p><strong>Results: </strong>Over a median 95.0-month follow-up, there were 1870 all-cause deaths and 579 cardiovascular disease-related deaths. Our findings indicate a J-shaped association between the AIP and ACM (threshold = 0.0905); specifically, when baseline AIP exceeded 0.0905, a significant positive association with ACM emerged (hazard ratio, HR (95% confidence interval, CI): 1.61(1.08-2.37)). However, after adjusting for confounders, the relationship between AIP and CVM was not statistically significant (HR 1.31, 95% CI 0.93-1.86). Notably, in the 40-60-year age group, AIP was significantly positively associated with ACM and CVM, with HRs and 95% CIs of 1.51 (1.08v2.10) and 2.63 (1.39-4.98), respectively.</p><p><strong>Conclusions: </strong>A J-shaped relationship was observed between baseline AIP levels and ACM within the general US population, with a threshold of 0.0905. Moreover, AIP could potentially be an effective predictor for future ACM or CVM, particularly among individuals aged 40-60. Further investigation is warranted to corroborate these findings.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery.","authors":"Massimo Nunes, Mare Vlok, Amy Proal, Douglas B Kell, Etheresia Pretorius","doi":"10.1186/s12933-024-02315-x","DOIUrl":"10.1186/s12933-024-02315-x","url":null,"abstract":"<p><p>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition that is characterized by unresolved fatigue, post-exertion symptom exacerbation (PESE), cognitive dysfunction, orthostatic intolerance, and other symptoms. ME/CFS lacks established clinical biomarkers and requires further elucidation of disease mechanisms. A growing number of studies demonstrate signs of hematological and cardiovascular pathology in ME/CFS cohorts, including hyperactivated platelets, endothelial dysfunction, vascular dysregulation, and anomalous clotting processes. To build on these findings, and to identify potential biomarkers that can be related to pathophysiology, we measured differences in protein expression in platelet-poor plasma (PPP) samples from 15 ME/CFS study participants and 10 controls not previously infected with SARS-CoV-2, using DIA LC-MS/MS. We identified 24 proteins that are significantly increased in the ME/CFS group compared to the controls, and 21 proteins that are significantly downregulated. Proteins related to clotting processes - thrombospondin-1 (important in platelet activation), platelet factor 4, and protein S - were differentially expressed in the ME/CFS group, suggestive of a dysregulated coagulation system and abnormal endothelial function. Complement machinery was also significantly downregulated, including C9 which forms part of the membrane attack complex. Additionally, we identified a significant upregulation of lactotransferrin, protein S100-A9, and an immunoglobulin variant. The findings from this experiment further implicate the coagulation and immune system in ME/CFS, and bring to attention the pathology of or imposed on the endothelium. This study highlights potential systems and proteins that require further research with regards to their contribution to the pathogenesis of ME/CFS, symptom manifestation, and biomarker potential, and also gives insight into the hematological and cardiovascular risk for ME/CFS individuals affected by diabetes mellitus.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential anti-arrhythmic effect of SGLT2 inhibitors.","authors":"Hong-Yi Duan, Hector Barajas-Martinez, Charles Antzelevitch, Dan Hu","doi":"10.1186/s12933-024-02312-0","DOIUrl":"10.1186/s12933-024-02312-0","url":null,"abstract":"<p><p>Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) were initially recommended as oral anti-diabetic drugs to treat type 2 diabetes (T2D), by inhibiting SGLT2 in proximal tubule and reduce renal reabsorption of sodium and glucose. While many clinical trials demonstrated the tremendous potential of SGLT2i for cardiovascular diseases. 2022 AHA/ACC/HFSA guideline first emphasized that SGLT2i were the only drug class that can cover the entire management of heart failure (HF) from prevention to treatment. Subsequently, the antiarrhythmic properties of SGLT2i have also attracted attention. Although there are currently no prospective studies specifically on the anti-arrhythmic effects of SGLT2i. We provide clues from clinical and fundamental researches to identify its antiarrhythmic effects, reviewing the evidences and mechanism for the SGLT2i antiarrhythmic effects and establishing a novel paradigm involving intracellular sodium, metabolism and autophagy to investigate the potential mechanisms of SGLT2i in mitigating arrhythmias.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of the association between triglyceride-glucose index and coronary artery disease severity across different glucose metabolism states: a large-scale cross-sectional study from an Asian cohort.","authors":"Sheng Zhao, Zuoxiang Wang, Ping Qing, Minghui Li, Qingrong Liu, Xuejie Pang, Keke Wang, Xiaojin Gao, Jie Zhao, Yongjian Wu","doi":"10.1186/s12933-024-02355-3","DOIUrl":"10.1186/s12933-024-02355-3","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose (TyG) index is associated with the development and prognosis of coronary artery disease (CAD). However, the impact of the TyG index on CAD severity across different glucose metabolism states exhibits significant disparities in previous research.</p><p><strong>Methods: </strong>This cross-sectional study comprised 10,433 participants from a prospective cohort. Participants were categorized into four groups based on glucose metabolism state: normal glucose regulation (NGR), prediabetes (pre-DM), diabetes mellitus (DM) without insulin prescribed (Rx), and DM with insulin Rx. The TyG index was determined by the following formula: Ln [TG (mg/dL) × FPG (mg/dL) / 2], where TG is triglycerides and FPG is fasting plasm glucose. Statistical methods such as binary logistic regression, interaction analysis, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were employed to analyze the relationship between the TyG index and CAD severity across the entire population and glucose metabolism subgroups. Mediation analysis was conducted to examine the mediating effects of glycated hemoglobin (HbA1c) on these relationships. Sensitivity analysis was performed to ensure the robustness of the findings.</p><p><strong>Results: </strong>Multivariable logistic regression analysis revealed a significant positive association between the TyG index and multi-vessel CAD in the entire population (OR: 1.34; 95% CI: 1.22-1.47 per 1-unit increment). Subgroup analysis demonstrated consistent positive associations in the NGR, pre-DM, and DM non-insulin Rx groups, with the highest OR observed in the NGR group (OR: 1.67; 95% CI: 1.3-2.14 per 1-unit increment). No correlation was found in the DM with insulin Rx subgroup. RCS analyses indicated the distinct dose-response relationships across different glucose metabolism subgroups. Including the TyG index in the established model slightly improved the predictive accuracy, particularly in the NGR group. Mediation analyses showed varying mediating effects of HbA1c among different glucose metabolism subgroups. Sensitivity analysis confirmed the robustness of the aforementioned relationships in the new-onset CAD population and in individuals not using antilipidemic medications.</p><p><strong>Conclusions: </strong>The TyG index positively associated with CAD severity across all glucose metabolism states, except for individuals receiving insulin treatment. Moreover, it might serve as a supplementary noninvasive predictor of CAD severity in addition to established factors, especially in NGR patients.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation-derived biological age and long-term mortality risk in subjects with type 2 diabetes.","authors":"Jacopo Sabbatinelli, Angelica Giuliani, Katarzyna Malgorzata Kwiatkowska, Giulia Matacchione, Alessia Belloni, Deborah Ramini, Francesco Prattichizzo, Valeria Pellegrini, Francesco Piacenza, Elena Tortato, Anna Rita Bonfigli, Davide Gentilini, Antonio Domenico Procopio, Paolo Garagnani, Fabiola Olivieri, Giuseppe Bronte","doi":"10.1186/s12933-024-02351-7","DOIUrl":"10.1186/s12933-024-02351-7","url":null,"abstract":"<p><strong>Background: </strong>Individuals with type 2 diabetes (T2D) face an increased mortality risk, not fully captured by canonical risk factors. Biological age estimation through DNA methylation (DNAm), i.e. the epigenetic clocks, is emerging as a possible tool to improve risk stratification for multiple outcomes. However, whether these tools predict mortality independently of canonical risk factors in subjects with T2D is unknown.</p><p><strong>Methods: </strong>Among a cohort of 568 T2D patients followed for 16.8 years, we selected a subgroup of 50 subjects, 27 survived and 23 deceased at present, passing the quality check and balanced for all risk factors after propensity score matching. We analyzed DNAm from peripheral blood leukocytes using the Infinium Human MethylationEPIC BeadChip (Illumina) to evaluate biological aging through previously validated epigenetic clocks and assess the DNAm-estimated levels of selected inflammatory proteins and blood cell counts. We tested the associations of these estimates with mortality using two-stage residual-outcome regression analysis, creating a reference model on data from the group of survived patients.</p><p><strong>Results: </strong>Deceased subjects had higher median epigenetic age expressed with DNAmPhenoAge algorithm (57.49 [54.72; 60.58] years. vs. 53.40 [49.73; 56.75] years; p = 0.012), and accelerated DunedinPoAm pace of aging (1.05 [1.02; 1.11] vs. 1.02 [0.98; 1.06]; p = 0.012). DNAm PhenoAge (HR 1.16, 95% CI 1.05-1.28; p = 0.004) and DunedinPoAm (HR 3.65, 95% CI 1.43-9.35; p = 0.007) showed an association with mortality independently of canonical risk factors. The epigenetic predictors of 3 chronic inflammation-related proteins, i.e. CXCL10, CXCL11 and enRAGE, C-reactive protein methylation risk score and DNAm-based estimates of exhausted CD8 + T cell counts were higher in deceased subjects when compared to survived.</p><p><strong>Conclusions: </strong>These findings suggest that biological aging, as estimated through existing epigenetic tools, is associated with mortality risk in individuals with T2D, independently of common risk factors and that increased DNAm-surrogates of inflammatory protein levels characterize deceased T2D patients. Replication in larger cohorts is needed to assess the potential of this approach to refine mortality risk in T2D.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between triglyceride glucose-waist height ratio index and cardiovascular disease in middle-aged and older Chinese individuals: a nationwide cohort study.","authors":"Qiushi Ren, Yang Huang, Quan Liu, Tongxin Chu, Gang Li, Zhongkai Wu","doi":"10.1186/s12933-024-02336-6","DOIUrl":"10.1186/s12933-024-02336-6","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose (TyG) index and its combination with obesity indicators can predict cardiovascular diseases (CVD). However, there is limited research on the relationship between changes in the triglyceride glucose-waist height ratio (TyG-WHtR) and CVD. Our study aims to investigate the relationship between the change in the TyG-WHtR and the risk of CVD.</p><p><strong>Methods: </strong>Participants were from the China Health and Retirement Longitudinal Study (CHARLS). CVD was defined as self-reporting heart disease and stroke. Participants were divided into three groups based on changes in TyG-WHtR using K-means cluster analysis. Multivariable binary logistic regression analysis was used to examine the association between different groups (based on the change of TyG-WHtR) and CVD. A restricted cubic spline (RCS) regression model was used to explore the potential nonlinear association of the cumulative TyG-WHtR and CVD events.</p><p><strong>Results: </strong>During follow-up between 2015 and 2020, 623 (18.8%) of 3312 participants developed CVD. After adjusting for various potential confounders, compared to the participants with consistently low and stable TyG-WHtR, the risk of CVD was significantly higher in participants with moderate and increasing TyG-WHtR (OR 1.28, 95%CI 1.01-1.63) and participants with high TyG-WHtR with a slowly increasing trend (OR 1.58, 95%CI 1.16-2.15). Higher levels of cumulative TyG-WHtR were independently associated with a higher risk of CVD events (per SD, OR 1.27, 95%CI 1.12-1.43).</p><p><strong>Conclusions: </strong>For middle-aged and older adults, changes in the TyG-WHtR are independently associated with the risk of CVD. Maintaining a favorable TyG index, effective weight management, and a reasonable waist circumference contribute to preventing CVD.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11241990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of empagliflozin on total myocardial infarction events by type and additional coronary outcomes: insights from the randomized EMPA-REG OUTCOME trial.","authors":"David Fitchett, Bernard Zinman, Silvio E Inzucchi, Christoph Wanner, Stefan D Anker, Stuart Pocock, Michaela Mattheus, Ola Vedin, Søren S Lund","doi":"10.1186/s12933-024-02328-6","DOIUrl":"10.1186/s12933-024-02328-6","url":null,"abstract":"<p><strong>Background: </strong>The effect of empagliflozin, a sodium-glucose-co-transporter-2 inhibitor, on risk for myocardial infarction has not been fully characterized.</p><p><strong>Methods: </strong>This study comprised prespecified and post-hoc analyses of the EMPA-REG OUTCOME trial in which 7020 people with type 2 diabetes (T2D) and cardiovascular disease [mostly atherosclerotic (ASCVD)] were randomized to empagliflozin or placebo and followed for a median 3.1 years. We assessed the effect of empagliflozin on total (first plus recurrent) events of centrally adjudicated fatal and non-fatal myocardial infarction (MI) using a negative binomial model with robust confidence intervals (CI) that preserves randomization and accounts for the within-patient correlation of multiple events. Post hoc, we analyzed types of MI: type 1 (related to plaque-rupture/thrombus), type 2 (myocardial supply-demand imbalance), type 3 (sudden-death related, i.e. fatal MI), type 4 (percutaneous coronary intervention-related), and type 5 (coronary artery bypass graft-related). MIs could be assigned to > 1 type.</p><p><strong>Results: </strong>There were 421 total MIs (including recurrent); 299, 86, 26, 19, and 1 were classified as type 1, 2, 3, 4, and 5 events, respectively. Overall, empagliflozin reduced the risk of total MI events by 21% [rate ratio for empagliflozin vs. placebo, 0.79 (95% CI, 0.620-0.998), P = 0.0486], largely driven by its effect on type 1 [rate ratio, 0.79 (95% CI, 0.61-1.04)] and type 2 MIs [rate ratio, 0.67 (95% CI, 0.41-1.10)].</p><p><strong>Conclusions: </strong>In T2D patients with ASCVD, empagliflozin reduced the risk of MIs, with consistent effects across the two most common etiologies, i.e. type 1 and 2.</p><p><strong>Trail registration: </strong>URL: https://www.</p><p><strong>Clinicaltrials: </strong>gov ; Unique identifier: NCT01131676.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11241944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miPEP31 alleviates Ang II-induced hypertension in mice by occupying Cebpα binding sites in the pri-miR-31 promoter.","authors":"Xiangxiao Li, Hong Zhou, Pengfei Lu, Zilong Fang, Guangzheng Shi, Xinran Tong, Wendong Chen, Gonghao Jiang, Peili Zhang, Jingyan Tian, Qun Li","doi":"10.1186/s12933-024-02337-5","DOIUrl":"10.1186/s12933-024-02337-5","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown that peptides encoded by noncoding RNAs (ncRNAs) can be used as peptide drugs to alleviate diseases. We found that microRNA-31 (miR-31) is involved in the regulation of hypertension and that the peptide miPEP31, which is encoded by the primary transcript of miR-31 (pri-miR-31), can inhibit miR-31 expression. However, the role and mechanism of miPEP31 in hypertension have not been elucidated.</p><p><strong>Methods: </strong>miPEP31 expression was determined by western blot analysis. miPEP31-deficient mice (miPEP31^-/-) were used, and synthetic miPEP31 was injected into Ang II-induced hypertensive mice. Blood pressure was monitored through the tail-cuff method. Histological staining was used to evaluate renal damage. Regulatory T (T_reg) cells were assessed by flow cytometry. Differentially expressed genes were analysed through RNA sequencing. The transcription factors were predicted by JASPAR. Luciferase reporter and electrophoretic mobility shift assays (EMSAs) were used to determine the effect of pri-miR-31 on the promoter activity of miPEP31. Images were taken to track the entry of miPEP31 into the cell.</p><p><strong>Results: </strong>miPEP31 is endogenously expressed in target organs and cells related to hypertension. miPEP31 deficiency exacerbated but exogenous miPEP31 administration mitigated the Ang II-induced systolic blood pressure (SBP) elevation, renal impairment and T_reg cell decreases in the kidney. Moreover, miPEP31 deletion increased the expression of genes related to Ang II-induced renal fibrosis. miPEP31 inhibited the transcription of miR-31 and promoted T_reg differentiation by occupying the Cebpα binding site. The minimal functional domain of miPEP31 was identified and shown to regulate miR-31.</p><p><strong>Conclusion: </strong>miPEP31 was identified as a potential therapeutic peptide for treating hypertension by promoting T_reg cell differentiation in vivo. Mechanistically, we found that miPEP31 acted as a transcriptional repressor to specifically inhibit miR-31 transcription by competitively occupying the Cebpα binding site in the pri-miR-31 promoter. Our study highlights the significant therapeutic effect of miPEP31 on hypertension and provides novel insight into the role and mechanism of miPEPs.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11241881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic score for insulin resistance (METS-IR) predicts all-cause and cardiovascular mortality in the general population: evidence from NHANES 2001-2018.","authors":"Mingxuan Duan, Xi Zhao, Shaolin Li, Guangrui Miao, Linpeng Bai, Qingyang Zhang, Wenxuan Yang, Xiaoyan Zhao","doi":"10.1186/s12933-024-02334-8","DOIUrl":"10.1186/s12933-024-02334-8","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of obesity-associated insulin resistance (IR) is increasing along with the increase in obesity rates. In this study, we compared the predictive utility of four alternative indexes of IR [triglyceride glucose index (TyG index), metabolic score for insulin resistance (METS-IR), the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and homeostatic model assessment of insulin resistance (HOMA-IR)] for all-cause mortality and cardiovascular mortality in the general population based on key variables screened by the Boruta algorithm. The aim was to find the best replacement index of IR.</p><p><strong>Methods: </strong>In this study, 14,653 participants were screened from the National Health and Nutrition Examination Survey (2001-2018). And TyG index, METS-IR, TG/HDL-C and HOMA-IR were calculated separately for each participant according to the given formula. The predictive values of IR replacement indexes for all-cause mortality and cardiovascular mortality in the general population were assessed.</p><p><strong>Results: </strong>Over a median follow-up period of 116 months, a total of 2085 (10.23%) all-cause deaths and 549 (2.61%) cardiovascular disease (CVD) related deaths were recorded. Multivariate Cox regression and restricted cubic splines analysis showed that among the four indexes, only METS-IR was significantly associated with both all-cause and CVD mortality, and both showed non-linear associations with an approximate \"U-shape\". Specifically, baseline METS-IR lower than the inflection point (41.33) was negatively associated with mortality [hazard ratio (HR) 0.972, 95% CI 0.950-0.997 for all-cause mortality]. In contrast, baseline METS-IR higher than the inflection point (41.33) was positively associated with mortality (HR 1.019, 95% CI 1.011-1.026 for all-cause mortality and HR 1.028, 95% CI 1.014-1.043 for CVD mortality). We further stratified the METS-IR and showed that significant associations between METS-IR levels and all-cause and cardiovascular mortality were predominantly present in the nonelderly population aged < 65 years.</p><p><strong>Conclusions: </strong>In conjunction with the results of the Boruta algorithm, METS-IR demonstrated a more significant association with all-cause and cardiovascular mortality in the U.S. population compared to the other three alternative IR indexes (TyG index, TG/HDL-C and HOMA-IR), particularly evident in individuals under 65 years old.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}