Cardiovascular Diabetology最新文献

{"title":"Correction: Insights into the complex relationship between triglyceride glucose-waist height ratio index, mean arterial pressure, and cardiovascular disease: a nationwide prospective cohort study.","authors":"Jie Xu, Dihui Cai, Yuheng Jiao, Yingying Liao, Yinyin Shen, Yunli Shen, Wei Han","doi":"10.1186/s12933-025-02728-2","DOIUrl":"10.1186/s12933-025-02728-2","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"214"},"PeriodicalIF":8.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076097","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 effects of SGLT2i on cardiac metabolism in patients with HFpEF: Fact or fiction?","authors":"Francesca Cinti, Renzo Laborante, Luigi Cappannoli, Cassandra Morciano, Shawn Gugliandolo, Alfredo Pontecorvi, Francesco Burzotta, Maria Donniacuo, Donato Cappetta, Giuseppe Patti, Andrea Giaccari, Domenico D'Amario","doi":"10.1186/s12933-025-02767-9","DOIUrl":"https://doi.org/10.1186/s12933-025-02767-9","url":null,"abstract":"<p><p>The rising prevalence of Type 2 diabetes (T2D) has been closely associated with an increased incidence of cardiovascular diseases, particularly heart failure with preserved ejection fraction (HFpEF). Cardiometabolic disturbances in T2D, such as insulin resistance, hyperglycemia, and dyslipidemia, contribute to both microvascular and macrovascular complications, thereby intensifying the risk of heart failure. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), initially developed as glucose-lowering agents for T2D, have demonstrated promising cardiovascular benefits in patients with heart failure, including those with preserved ejection fraction (HFpEF), regardless of T2D status. These benefits include reduced heart failure hospitalization rates and improvements in various metabolic parameters. This review aims to critically examine the effects of SGLT2i on cardiac metabolism in HFpEF, evaluating whether the observed benefits can truly be attributed to their impact on myocardial energy regulation or whether they represent other, potentially confounding, mechanisms. We will focus on the key metabolic processes possibly modulated by SGLT2i, including myocardial glucose utilization, fatty acid oxidation, and mitochondrial function, and explore their effects on heart failure pathophysiology. Additionally, we will address the role of SGLT2i in other pathogenetic factors involved in HFpEF, such as sodium and fluid balance, inflammation, and fibrosis, and question the extent to which these mechanisms contribute to the observed clinical benefits. By synthesizing the current evidence, this review will provide an in-depth analysis of the mechanisms through which SGLT2i may influence cardiac metabolism in HFpEF, assessing whether their effects are supported by robust scientific data or remain speculative. We will also discuss the potential for personalized treatment strategies, based on individual patient characteristics, to optimize the therapeutic benefits of SGLT2i in managing both T2D and cardiovascular risk. This review seeks to clarify the true clinical utility of SGLT2i in the management of cardiometabolic diseases and HFpEF, offering insights into their role in improving long-term cardiovascular outcomes.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"208"},"PeriodicalIF":8.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076175","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":"Dysregulated inflammation, oxidative stress, and protein quality control in diabetic HFpEF: unraveling mechanisms and therapeutic targets.","authors":"Simin Delalat, Innas Sultana, Hersh Osman, Marcel Sieme, Saltanat Zhazykbayeva, Melissa Herwig, Heidi Budde, Árpád Kovács, Mustafa Kaçmaz, Eda Göztepe, Natalie Borgmann, Gelareh Shahriari, Benjamin Sasko, Jan Wintrich, Peter Haldenwang, Wolfgang E Schmidt, Wiebke Fenske, Muchtiar Khan, Kornelia Jaquet, Andreas Mügge, Domokos Máthé, Viktória E Tóth, Zoltán V Varga, Péter Ferdinandy, Ibrahim El-Battrawy, Loek van Heerebeek, Nazha Hamdani","doi":"10.1186/s12933-025-02734-4","DOIUrl":"https://doi.org/10.1186/s12933-025-02734-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Type 2 diabetes mellitus (T2DM) represents a significant risk factor for cardiovascular disease, particularly heart failure with preserved ejection fraction (HFpEF). HFpEF predominantly affects elderly individuals and women, and is characterized by dysfunctions associated with metabolic, inflammatory, and oxidative stress pathways. Despite HFpEF being the most prevalent heart failure phenotype in patients with T2DM, its underlying pathophysiological mechanisms remain inadequately elucidated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to investigate the effects of diabetes mellitus on myocardial inflammation, oxidative stress, and protein quality control (PQC) mechanisms in HFpEF, with particular emphasis on insulin signaling, autophagy, and chaperone-mediated stress responses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted an analysis of left ventricular myocardial tissue from HFpEF patients, both with and without diabetes, employing a range of molecular, biochemical, and functional assays. The passive stiffness of cardiomyocytes (Fpassive) was assessed in demembranated cardiomyocytes before and after implementing treatments aimed at reducing inflammation (IL-6 inhibition), oxidative stress (Mito-TEMPO), and enhancing PQC (HSP27, HSP70). Inflammatory markers (NF-κB, IL-6, TNF-α, ICAM-1, VCAM-1, NLRP3), oxidative stress markers (ROS, GSH/GSSG ratio, lipid peroxidation), and components of signaling pathways (PI3K/AKT/mTOR, AMPK, MAPK, and PKG) were evaluated using western blotting, immunofluorescence, and ELISA techniques.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Hearts from diabetic HFpEF patients exhibited significantly heightened inflammation, characterized by the upregulation of NF-κB, IL-6, and the NLRP3 inflammasome. This increase in inflammation was accompanied by elevated oxidative stress, diminished nitric oxide (NO) bioavailability, and impaired activation of the NO-sGC-cGMP-PKG signaling pathway. Notably, dysregulation of insulin signaling was observed, as indicated by decreased AKT phosphorylation and impaired autophagy regulation mediated by AMPK and mTOR. Additionally, PQC dysfunction was evidenced by reduced expression levels of HSP27 and HSP70, which correlated with increased cardiomyocyte passive stiffness. Targeted therapeutic interventions effectively reduced Fpassive, with IL-6 inhibition, Mito-TEMPO, and HSP administration leading to improvements in cardiomyocyte mechanical properties.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The findings of this study elucidate a mechanistic relationship among diabetes, inflammation, oxidative stress, and PQC impairment in the context of HFpEF. Therapeutic strategies that target these dysregulated pathways, including IL-6 inhibition, mitochondrial antioxidants, and chaperone-mediated protection, may enhance myocardial function in HFpEF patients with T2DM. Addressing these molecular dysfunctions could facilitate the development of novel interventions specifically tailored ","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"211"},"PeriodicalIF":8.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076099","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":"Use of an insulin titration protocol based on continuous glucose monitoring in postoperative cardiac surgery patients with type 2 diabetes and prediabetes: a randomized controlled trial.","authors":"Sun-Joon Moon, Min-Su Kim, Yun Tae Kim, Ha-Eun Lee, Young-Woo Lee, Su-Ji Lee, Euy-Suk Chung, Cheol-Young Park","doi":"10.1186/s12933-025-02747-z","DOIUrl":"10.1186/s12933-025-02747-z","url":null,"abstract":"<p><strong>Background: </strong>Maintaining optimal glucose control is critical for postoperative care cardiac surgery patients. Continuous glucose monitoring (CGM) in this setting remains understudied. We evaluated the efficacy of CGM with a specialized titration protocol in cardiac surgery patients with type 2 diabetes (T2D) and prediabetes.</p><p><strong>Methods: </strong>In this randomized-controlled trial, 54 cardiac surgery patients were randomized one day post-surgery, with 27 CGM and 25 point-of-care (POC) patients completing the study. The CGM group used Dexcom G6 with a CGM-specialized titration protocol, while the POC group used standard monitoring with blinded CGM. The primary outcome was time-in-range (TIR) 100-180 mg/dL for 7 days post-surgery. Secondary outcomes included various glycemic metrics and surgical outcomes. Multiple comparison adjustments were performed using false-discovery-rate (FDR).</p><p><strong>Results: </strong>Thirty-one (59.6%) had diabetes and 21 (40.4%) had prediabetes. While TIR 100-180 mg/dL showed no difference (74.7% vs. 71.6%, FDR-adjusted p = 0.376), the CGM group demonstrated improvements in TIR 70-180 mg/dL (83.8% vs. 75.8%, FDR-adjusted p = 0.026), time-in-tight-range (TITR) 100-140 mg/dL (46.3% vs. 36.3%, FDR-adjusted p = 0.018), and TITR 70-140 mg/dL (55.3% vs. 40.5%, FDR-adjusted p = 0.003). Both groups maintained very low rates of time below range (< 70 mg/dL: 0.03% vs. 0.18%, FDR-adjusted p = 0.109). The CGM group showed lower postoperative atrial fibrillation (AF) (18.8% vs. 55.6%, FDR-adjusted p = 0.04999).</p><p><strong>Conclusion: </strong>While the primary outcome was not achieved, CGM with a specialized titration protocol demonstrated safe glycemic control with improvements in TIR 70-180 mg/dL and TITRs in cardiac surgery patients with T2D and prediabetes. The observed reduction in postoperative AF warrants further investigation.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT06275971.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"210"},"PeriodicalIF":8.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076176","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":"Sacubitril/Valsartan attenuates progression of diabetic cardiomyopathy through immunomodulation properties: an opportunity to prevent progressive disease.","authors":"Narainrit Karuna, Lauren Kerrigan, Kevin Edgar, Mark Ledwidge, Ken McDonald, David J Grieve, Chris J Watson","doi":"10.1186/s12933-025-02741-5","DOIUrl":"https://doi.org/10.1186/s12933-025-02741-5","url":null,"abstract":"<p><strong>Background and aims: </strong>Diabetic cardiomyopathy (DbCM) is recognised as a key mediator and determinant of heart failure (HF), particularly HF with preserved ejection fraction (HFpEF). Improved understanding of mechanisms underlying transition from early-stage DbCM to HFpEF will inform innovative evidence-based treatment approaches, which are urgently required to alleviate increasing disease burden. This study aimed to determine whether inhibition of neprilysin activity by Sacubitril/Valsartan in both experimental and clinical DbCM attenuates adverse remodelling through promotion of cardioprotective signalling.</p><p><strong>Methods and results: </strong>Sacubitril/Valsartan effectively reduced plasma neprilysin activity in both diabetic patients with pre-clinical HFpEF from the PARABLE trial (baseline (Val n = 25; Sac/Val n = 35) and 3 months after treatment (Val n = 21/25; Sac/Val n = 33/35)) and DbCM (high-fat diet and streptozotocin) mice. Plasma neprilysin activity at baseline was correlated with worsening cardiac performance at 18 months indicated by left atrial stiffness index in patients (n = 44/60), whilst diastolic dysfunction and pathological remodelling in DbCM mice were improved by Sacubitril/Valsartan, but not Valsartan. snRNA-sequencing showed that progressive experimental DbCM is characterised by chronic low-grade inflammation, reflected by increased infiltration of pro-inflammatory monocytes (Ccr2⁺ Ly6c^hi) and reduction in MHC-II macrophages, which was prevented by Sacubitril/Valsartan. Informatics analysis implicated IRF7 as a central mediator of Sacubitril/Valsartan-induced immunomodulation in DbCM, whilst treatment of M2-like pro-repair macrophages with the neprilysin inhibitor, LBQ657 and Valsartan suppressed glucose-induced IRF7 expression and paracrine activation of cardiac fibroblast differentiation in vitro.</p><p><strong>Conclusion: </strong>Immune cells are significantly involved in DbCM progression, impacting myocardial homeostasis and HF progression. Neprilysin inhibition by Sacubitril/Valsartan improved adverse cardiac remodelling in experimental DbCM through direct regulation of inflammation, highlighting immunomodulation as a novel mechanism underlying established its cardioprotective actions.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"206"},"PeriodicalIF":8.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075909","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":"How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studies.","authors":"Lin Hu, Jiayuan Li, Zihuan Tang, Peng Gong, Zongqi Chang, Chen Yang, Tianpei Ma, Shuang Jiang, Chunxia Yang, Tao Zhang","doi":"10.1186/s12933-025-02770-0","DOIUrl":"10.1186/s12933-025-02770-0","url":null,"abstract":"<p><strong>Background: </strong>Recent basic biological research found that obesity accelerates biological aging and increases cardiovascular disease (CVD) risk. However, there is still a lack of real-world population evidence. This study aimed to explore the potential mediation roles of biological age acceleration in the associations between different dimensions of obesity characterization and incident CVD.</p><p><strong>Methods: </strong>This international multi-cohort study included participants aged over 45 years with 3 waves longitudinal data from China Health and Retirement Longitudinal Study (CHARLS). China Health and Nutrition Survey (CHNS) was used to develop Klemera-Doubal method-biological age (KDM-BA), and the validation analysis was performed in UK Biobank (UKB) and Hongguang Elderly Health Examination Cohort (HEHEC). Obesity indices including body mass index (BMI), waist circumference (WC), waist height ratio (WtHR), body roundness index (BRI) for body shape; Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP) for visceral fat accumulation; triglyceride-glucose index (TyG) and its derivatives (TyG-BMI, TyG-WC, TyG-WtHR) for metabolic function were used to measure obesity across different dimensions. Biological age acceleration was evaluated by the classic KDM-BA acceleration (KDM-BAacc). Causal mediation analyses assessed the role of biological age acceleration in mediating obesity and incident CVD.</p><p><strong>Results: </strong>In CHARLS, the median follow-up period was 9.00 years, with a baseline age of 58 (52, 65) years. Obesity, KDM-BAacc, and CVD were all significantly associated with each other. For each 1-year increase in KDM-BAacc, the risk of incident stroke, heart disease and CVD increased by 68% (OR 1.68, 95% CI 1.35-2.09), 35% (OR 1.35, 95% CI 1.15-1.59), and 44% (OR 1.44, 95% CI 1.25-1.65), respectively. KDM-BAacc mediated the associations between BMI, WC, WtHR, BRI, CVAI, LAP, TyG-BMI, TyG-WC, TyG-WtHR, with CVD, with the mediation proportions ranging from 10.03 to 25.46%. However, the mediating effect was significant mostly in middle-aged individuals aged 45-65 years. Furthermore, sex differences existed in the mediation mechanisms. Biological age acceleration strongly mediated body shape indices and incident CVD in males, whereas in females, it predominantly mediated visceral fat accumulation and metabolic function dimensions with incident CVD. Similar main results were found in UKB and HEHEC.</p><p><strong>Conclusions: </strong>Biological age acceleration partially mediates the relationship between obesity and incident CVD. This temporal evidence firstly validated the mediation pathway based on international cohorts, emphasizing the importance of addressing biological aging processes in population aged 45-65 years while providing sex-specific obesity intervention strategies to prevent CVD.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"209"},"PeriodicalIF":8.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074956","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":"Atherogenic lipid parameters in people with normal glucose tolerance: implications from elevated 1-hour post-load plasma glucose.","authors":"Chunyu Yang, Xin Chai, Yachen Wang, Di Li, Dongli Zhu, Kaipeng Liang, Jinping Wang, Zhiwei Yang, Qiuhong Gong, Juan Zhang, Ruitai Shao","doi":"10.1186/s12933-025-02722-8","DOIUrl":"https://doi.org/10.1186/s12933-025-02722-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Existing evidence suggests that elevated 1-hour post-load plasma glucose (1-h PG ≥ 8.6 mmol/L) during an oral glucose tolerance test (OGTT) is associated with atherogenic lipid parameters which are linked to an increased risk of cardiovascular disease (CVD). However, it remains unclear whether normal glucose tolerance (NGT) individuals with elevated 1-h PG (NGT-1hPG-high) should still be considered low-risk. Therefore, this study aims to demonstrate comprehensive lipid characteristics in individuals with different glycemic status stratified by 1-h PG, with a particular focus on those with NGT-1hPG-high.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This cross-sectional study included individuals aged 25-55 years with high-risk of diabetes from the Daqing Diabetes Prevention Study II (Daqing DPS-II). Individuals were categorized into different glycemic status based on the World Health Organization's 1999 criteria and the International Diabetes Federation's 2024 position statement on 1-h PG. Traditional (TC, TG, HDL-C, LDL-C) and non-traditional lipid parameters [ApoA-1, ApoB, sdLDL-C, Lp(a), non-HDL-C, remnant cholesterol (RC), ApoB/ApoA-1, LDL-C/ApoB] were measured. Dyslipidemia was defined according to the 2023 Chinese Guidelines for Lipid Management. The China-PAR equation was used to estimate 10-year CVD risk. Spearman's correlation coefficients were calculated to evaluate the correlation between lipid parameters and 10-year CVD risk. Logistic and multiple linear regression models were performed to assess the association between 1-h PG and dyslipidemia as well as lipid parameters adjusting for covariates.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 2 469 individuals, 22.7% had NGT with normal 1-h PG (NGT-1hPG-normal), 19.9% had NGT-1hPG-high, 2.6% had prediabetes with normal 1-h PG (PDM-1hPG-normal), 34.2% had prediabetes with elevated 1-h PG (PDM-1hPG-high), and 20.6% had newly diagnosed diabetes. The prevalence of dyslipidemia did not significantly differ between NGT-1hPG-high and PDM-1hPG-high (OR = 1.13, 95%CI: 0.88-1.44, P &gt; 0.05). Higher 1-h PG levels were consistently associated with an atherogenic lipid profile, characterized by increased TC, TG, LDL-C, ApoB, sdLDL-C, non-HDL-C, RC and ApoB/ApoA-1, along with decreased ApoA-1, HDL-C and LDL-C/ApoB (all P &lt; 0.05). Among lipid parameters, TG, sdLDL-C, RC, ApoB/ApoA-1, LDL-C/ApoB and HDL-C showed the strongest correlation with 10-year CVD risk, with Spearman's correlation coefficients of 0.41, 0.38, 0.35, 0.31, - 0.37 and - 0.36, respectively. In the NGT-1hPG-high, TG, sdLDL-C, and ApoB/ApoA-1 levels were significantly higher, while HDL-C and LDL-C/ApoB levels were significantly lower compared to counterparts with NGT-1hPG-normal (all P &lt; 0.05). Moreover, except for TG and RC (both P &lt; 0.01), the majority of lipid parameter levels in NGT-1hPG-high did not significantly differ from those in PDM (all P &gt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;NGT-1hPG-high exhibited a simila","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"207"},"PeriodicalIF":8.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076066","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":"Extracellular vesicle-associated miR-515-5p from adipose tissue regulates placental metabolism and fetal growth in gestational diabetes mellitus.","authors":"Nanthini Jayabalan, Soumyalekshmi Nair, Andrew Lai, Katherin Scholz-Romero, Melissa Razo-Azamar, Valeska Ormazabal, Ratana Lim, Flavio Carrion, Dominic Guanzon, Gregory E Rice, Harold David McIntyre, Martha Lappas, Carlos Salomon","doi":"10.1186/s12933-025-02739-z","DOIUrl":"https://doi.org/10.1186/s12933-025-02739-z","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) affects 2-20% of pregnant women worldwide and is linked to fetal overgrowth, increased perinatal morbidity, and mortality, as well as a higher risk of developing cardiovascular disease later in life for mother and child. MicroRNAs (miRNAs), which regulate gene expression, can be transported within extracellular vesicles (EVs). Adipose tissue-derived EVs have been associated with changes in placental metabolism in GDM, potentially influencing cardiovascular health outcomes. This study aimed to evaluate the miRNA profile in EVs from omental adipose tissue in GDM and their effect on placental nutrient uptake and fetal growth.</p><p><strong>Methods: </strong>This case-control study included patients with normal glucose tolerance (NGT) and GDM. We conducted a miRNA expression profiling on omental adipose tissue and its derived EVs from women with NGT (n = 20) and GDM (n = 36). Trophoblast cells were utilized to assess the effect of EVs on glucose and fatty acid uptake, pro-inflammatory cytokine, and chemokine release. Double-stranded miRNA mimics were used to investigate the effect of selected miRNAs on trophoblast cells. Subsequently, the impact of EVs from NGT and GDM, as well as miR-515-5p, on in vivo glucose tolerance and fetal growth was assessed in pregnant mice.</p><p><strong>Results: </strong>Fifty-four miRNAs showed significant differences between EVs from the adipose tissue of NGT and GDM groups. EVs from GDM increased glucose uptake in trophoblast cells, whereas EVs from NGT increased the secretion of CXCL8, IL-6, CXCL1, CXCL4, and CXCL5 from trophoblasts compared to the effect without EVs. Specifically, miR-515-5p increased glucose uptake and abolished TNF-α-dependent increase in pro-inflammatory cytokines and chemokines from trophoblast cells. Injection of pregnant mice with EVs from NGT adipose tissue loaded with miR-515-5p resulted in increased fetal weight and glucose levels.</p><p><strong>Conclusion: </strong>miR-515-5p, specifically encapsulated within EVs from omental adipose tissue in GDM, regulates placental nutrient uptake, glucose homeostasis, and fetal growth.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"205"},"PeriodicalIF":8.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076174","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":"Diabetes mellitus aggravates myocardial inflammation and oxidative stress in aortic stenosis: a mechanistic link to HFpEF features.","authors":"Melissa Herwig, Marcel Sieme, Andrea Kovács, Muchtiar Khan, Andreas Mügge, Wolfgang E Schmidt, Ferhat Elci, Shan Sasidharan, Peter Haldenwang, Jan Wintrich, Benjamin Sasko, Ibrahim Akin, Máthé Domokos, Francesco Paneni, Ibrahim El-Battrawy, Zoltán V Varga, Francisca Saraiva, Adelino F Leite-Moreira, Péter Ferdinandy, Loek van Heerebeek, Inês Falcão-Pires, Nazha Hamdani","doi":"10.1186/s12933-025-02748-y","DOIUrl":"10.1186/s12933-025-02748-y","url":null,"abstract":"<p><strong>Background: </strong>Patients diagnosed with both aortic stenosis (AS) and diabetes mellitus (DM) encounter a distinctive set of challenges due to the interplay between these two conditions. This study aimed to investigate the effects of DM on the left ventricle in AS patients, specifically focusing on the inflammatory response, oxidative stress, and their implications for cardiomyocyte function, titin phosphorylation, and the nitric oxide (NO)-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway.</p><p><strong>Methods and results: </strong>Left ventricular myocardial biopsies (in total: n = 28) were obtained from patients with diabetic AS (n = 11) and compared with those from non-diabetic AS patients (n = 17). Enzyme-linked immunosorbent assay (ELISA) demonstrated significantly elevated levels of pro-inflammatory mediators, including high mobility group box protein 1 (HMGB1) and calprotectin, as well as receptors associated with the inflammatory response, such as Toll-like receptor 2 (TLR2), 4 (TLR4), and receptor for advanced glycation endproducts (RAGE). These were correlated with an enhanced NOD-like receptor protein 3 (NLRP3) inflammasome and the release of interleukins (IL) 1, 6, and 18 in diabetic AS patients compared to their non-diabetic counterparts. Additionally, in the diabetic AS cohort, there was an increase in oxidative stress markers (hydrogen peroxide (H₂O₂), 3-nitrotyrosine, lipid peroxidation (LPO), oxidative glutathione (GSSG)/reduced glutathione (GSH) ratio) within the myocardium and mitochondria, accompanied by impaired NO-sGC-cGMP-PKG signaling, decreased titin phosphorylation, and increased passive stiffness (F_passive) of cardiomyocytes relative to non-diabetic AS patients. In vitro anti-inflammatory treatment with an IL-6 inhibitor and antioxidant treatment with GSH effectively normalized the elevated F_passive observed in AS patients with DM to levels comparable to the non-diabetic group. Furthermore, treatment with PKG and the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin also resulted in a reduction of F_passive in cardiomyocytes from diabetic AS patients, although not to the levels observed in non-diabetic AS patients.</p><p><strong>Conclusion: </strong>DM exacerbates inflammation and oxidative stress in AS patients, leading to impaired NO-sGC-cGMP-PKG signaling and increased cardiomyocyte F_passive. These conditions are reminiscent of the pathophysiology of heart failure with preserved ejection fraction (HFpEF). These alterations can be ameliorated through anti-inflammatory and antioxidant therapies, indicating potential therapeutic strategies for diabetic patients suffering from AS.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"203"},"PeriodicalIF":8.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977299","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":"Correction: Deficiency in nucleoside diphosphate kinase B leads to endothelial activation of the hexosamine biosynthesis pathway and cardiac dysfunction.","authors":"Feng Shao, Johanna Wieland, Yixin Wang, Merve Keles, Zenghui Meng, Santosh Lomada, Miao Qin, Veronika Leiss, Abel Martin-Garrido, Manuela Fuhrmann, Yi Qiu, Felix A Trogisch, Christiane Vettel, Joerg Heineke, Yuxi Feng","doi":"10.1186/s12933-025-02759-9","DOIUrl":"10.1186/s12933-025-02759-9","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"204"},"PeriodicalIF":8.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977448","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}