Archives of Cardiovascular Diseases最新文献

{"title":"Mesp1 and Hes1 interplay controls early cardiac progenitor cell specification","authors":"Sinem Inal,&nbsp;Fabienne Lescroart,&nbsp;Francesca Rochais","doi":"10.1016/j.acvd.2025.03.035","DOIUrl":"10.1016/j.acvd.2025.03.035","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiac progenitors (CPs) arise early during gastrulation. CPs express transcription factor Mesp1 and contribute to all cardiac territories. Alteration in CP specification or migration leads to congenital heart defects (CHDs) affecting 1% of live births. We uncovered Mesp1 as a master regulator of early cardiovascular specification and differentiation (Lescroart et al., Science 2018; Lin et al., Nat Cell Biol 2022), and recently identified a crucial role for transcriptional repressor Hes1 in CP deployment (Rammah et al., Circ Res 2022). Indeed, Hes1 deletion results in embryonic lethality due to CHDs. Interestingly, Hes1 conditional deletion in Mesp1 lineage recapitulates the heart defects observed in Hes1 null embryos.</div></div><div><h3>Objective</h3><div>To investigate the mechanism of early CP specification by exploring Mesp1 and Hes1 possible interplay.</div></div><div><h3>Method</h3><div>In vitro mouse gastrulation model, gastruloid and mouse embryos were used to reveal expression levels and patterns of Mesp1 and Hes1 using fluorescent in situ hybridization technique, RNAscope. RNAseq and Chip-seq experiments were performed on Mesp1 gain-of-function (GOF) mESC line. ScRNAseq analysis was performed during gastruloid culture.</div></div><div><h3>Results</h3><div>RNAscope on mouse embryos revealed differential Hes1 expression during gastrulation. While Hes1 expression is high in FHF progenitors, starts to decline in SHF progenitors. RNAseq and Chip-seq data using Mesp1 GOF mESCs has shown downregulation of Hes1 by Mesp1. Using Mesp1 mutant embryos, we showed increased Hes1 expression in mesoderm supporting the previous data. ScRNAseq on gastruloids revealed coexpression of Mesp1 and Hes1 in CP subpopulations. We reproduced these results with RNAscope and uncovered similar expression patterns in different CPs that of embryos. Hes1 expression is detected in Hand1+ FHF progenitors and downregulated in Foxc2+ SHF progenitors. These results validate our in vivo and in vitro models and point out a role for Hes1 in early heart development that has not been reported.</div></div><div><h3>Conclusion</h3><div>Our data strongly support a role for Mesp1-Hes1 interplay in the regulation of early CP specification.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S188"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099591","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}

{"title":"Erythropoietin recapitulates ultrasound-assessed hemodynamic and morphological features of hypoxia-induced pulmonary hypertension in mice","authors":"Ghina Bouabout ,&nbsp;Julien Becker ,&nbsp;Emilie Peter-Thiebaut ,&nbsp;Mégane Denu ,&nbsp;Hugues Jacobs ,&nbsp;Benoit Petit Demoulière ,&nbsp;Yann Herault ,&nbsp;Laurent Monassier","doi":"10.1016/j.acvd.2025.03.015","DOIUrl":"10.1016/j.acvd.2025.03.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Pulmonary hypertension is characterized by increased pulmonary vascular resistances leading to right ventricular failure. Chronic hypoxia is a risk factor for PH. End-stage renal disease patients with chronic haemodialysis have increased risk of PH. Most of these are treated with erythropoietin (EPO) because of anaemia. Involvement EPO as causative of PH in controversial.</div></div><div><h3>Objective</h3><div>We investigated if an EPO treatment could reproduce hemodynamic and morphologic features of hypoxia-induced PH and whether endothelial progenitor cells mobilized in PH due to hypoxia, could be involved in EPO-induced PH.</div></div><div><h3>Method</h3><div>The first group of mice was treated with EPO for 2 and 4 weeks and the 2nd group of hypoxia (10%) was exposed during 2 and 4 weeks. Blood analysis, heart and valves remodeling and function were assessed by high frequency echocardiography (Vevo3100 from Visual sonics) using a linear MS440 and MS500 probe. Isovolumetric relaxation and contraction time were recorded with a pulsed-Doppler window placed at the tip of the leaflets valves and right ventricle strain was also evaluated. Blood pressure and heart rate were recorded. Right ventricular pressure, heart and lung histology and blood circulating endothelial progenitor cells were assessed after 2 weeks.</div></div><div><h3>Results</h3><div>The EPO treatment for 2 weeks and 4 weeks and hypoxia induce PH with an important increase in pulmonary and right ventricular pressure and RV/LV<!--> <!-->+<!--> <!-->septum size attested by pulmonary and peripheral vein pressure increases compared to normoxia animals. Similarly, the treatment with EPO or hypoxia in mice significantly alters the inferior vena cava (IVC) pulsatility index with a decrease in inspiratory fractional shortening. EPO and hypoxia groups show right ventricle hypertrophy as attested by an increased in RV/LV<!--> <!-->+<!--> <!-->septum weight ratio and pulmonary artery remodeling increased pulmonary wall vessel thickening of vessels with a diameter below 3–4<!--> <!-->μm (pre-acinar and intra-acinar pulmonary vessels) with an elastic fibrosis of alveolar vessels wall. EPO provoked an increase in the blood mobilization of endothelial progenitor cells at a similar extent than hypoxia.</div></div><div><h3>Conclusion</h3><div>EPO recapitulates hemodynamic features of hypoxia-induced pulmonary hypertension in mice when hematocrit is increased over the physiological range. Nevertheless a pharmacological effect not linked to hematopoiesis is discussed.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S178"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099089","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}

{"title":"Role of Miro1, the mitochondrial Rho GTPase, in cardiomyocyte function and heart homeostasis","authors":"Jean-Sébastien Vartanian-Grimaldi ,&nbsp;Zhenlin Li ,&nbsp;Gaëlle Revet ,&nbsp;Simon Alexandre ,&nbsp;Nathalie Mougenot ,&nbsp;Onnik Agbulut ,&nbsp;Rodriguez Anne-Marie","doi":"10.1016/j.acvd.2025.03.075","DOIUrl":"10.1016/j.acvd.2025.03.075","url":null,"abstract":"<div><h3>Introduction</h3><div>Mitochondria, which are mainly abundant in cardiomyocytes and whose dysfunction has been widely observed in cardiovascular disease, are increasingly being considered as potential therapeutic targets. The function of mitochondria is closely linked to their ability to move along microtubules to adapt their distribution, morphology and dynamics in response to the demands of the cell. The outer mitochondrial membrane protein Miro1 is a key regulator of mitochondrial motility by promoting the anchorage of mitochondria to the kinesin/dynein motor of the microtubules on which they move. The role of Miro1 in cardiomyocytes remains largely unknown.</div></div><div><h3>Objective</h3><div>In this study, we explored the role of Miro1 in the heart using cardiomyocyte-specific deletion of Miro1 in adult mice.</div></div><div><h3>Method</h3><div>We disrupted Miro1 in the adult heart using a heart-specific tamoxifen-inducible Cre recombinase. Two and five weeks after tamoxifen injection, mice were characterized via echocardiography, comprehensive morphological evaluation, metabolic analysis, and transcriptomic profiling.</div></div><div><h3>Results</h3><div>The disruption of Miro1 led to impaired left ventricular function with reduced contractility, subsequently progressing to dilated cardiomyopathy, as demonstrated by serial echocardiography, including tissue Doppler imaging. The cytoarchitecture of cardiomyocytes was altered and display altered mitochondrial architecture. Interestingly, these alterations were associated with an increased fibrosis (assessed by Sirius red staining). These functional and structural defects were preceded by early alterations in the cardiac gene expression program: major decreases in mRNA levels for cardiac α-actin, muscle creatine kinase, and calcium-handling genes and increases in mRNA levels for stress-induced genes such as beta-myosin heavy chain genes, atrial natriuretic factor and brain natriuretic peptide.</div></div><div><h3>Conclusion</h3><div>These results highlight the importance of Miro1 in the maintenance of heart homeostasis and function.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S208"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099219","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}

{"title":"Predictive factors of low cardiac output in patients hospitalized for intermediate-high-risk pulmonary embolism","authors":"Guillaume Faivre-Dupaigre","doi":"10.1016/j.acvd.2025.03.065","DOIUrl":"10.1016/j.acvd.2025.03.065","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;The prognosis of patients hospitalized for intermediate-high-risk pulmonary embolism (PE) varies, with an estimated mortality from 3 to 15%. New therapeutic strategies, such as half-dose fibrinolysis or percutaneous reperfusion techniques, are currently under evaluation in this patient group. The role of these therapeutic strategies remains to be defined.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To identify clinical and paraclinical factors associated with low cardiac output in patients hospitalized for intermediate-high-risk PE.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;This prospective observational study included patients hospitalized in cardiac intensive care unit for intermediate-high-risk PE at Lille University Hospital between April 2022 and April 2024. After measuring cardiac index (CI) by right heart catheterization, demographic, clinical, biological, and imaging data were described and compared between patients with CI&lt;!--&gt; &lt;!--&gt;≤&lt;!--&gt; &lt;!--&gt;2.5&lt;!--&gt; &lt;!--&gt;L/min/m&lt;sup&gt;2&lt;/sup&gt; and those with CI&lt;!--&gt; &lt;!--&gt;&gt;&lt;!--&gt; &lt;!--&gt;2.5&lt;!--&gt; &lt;!--&gt;L/min/m&lt;sup&gt;2&lt;/sup&gt;. Multivariate logistic regression analysis was performed to identify independent factors associated with low cardiac output.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among the 82 patients included, 53.7% had a CI&lt;!--&gt; &lt;!--&gt;≤&lt;!--&gt; &lt;!--&gt;2.5&lt;!--&gt; &lt;!--&gt;L/min/m&lt;sup&gt;2&lt;/sup&gt;. This group had biological signs of poor tolerance, including lower prothrombin time (77 vs. 84%, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.014), lower glomerular filtration rate (71 vs. 88&lt;!--&gt; &lt;!--&gt;L/min/m&lt;sup&gt;2&lt;/sup&gt;, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.003), and lower mixed venous oxygen saturation (57.4 vs. 68.6%, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.001). Patients with low cardiac output had more dilated right ventricles (RV diameter: 36 vs. 33&lt;!--&gt; &lt;!--&gt;mm, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.005), reduced RV contractility (TAPSE: 15 vs. 19&lt;!--&gt; &lt;!--&gt;mm, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.001; S’tdi wave: 8 vs. 11&lt;!--&gt; &lt;!--&gt;cm/s, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.001), higher estimated right atrial pressure on echocardiography (&lt;em&gt;P&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.001), and higher NT-proBNP levels (4366 vs. 2036&lt;!--&gt; &lt;!--&gt;μg/mL, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.001). The two independent predictive factors for low cardiac output were the S’tdi wave measurement and the echocardiographic estimation of right atrial pressure. Clinical parameters did not differ between the two groups. Non-invasive cardiac output measurement via transthoracic echocardiography (TTE) showed good correlation with invasive measurements and acceptable accuracy (mean error of&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;0.40&lt;!--&gt; &lt;!--&gt;L/min/m&lt;sup&gt;2&lt;/sup&gt;).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Half of the patients admitted for intermediate-high-risk PE have impaired cardiac output. Identifying these patients based only on clinical parameters is challenging. TTE appears to be the most effective tool for identifying the most severe cases, enabling the consideration of interventional or pharm","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S203"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099204","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}

{"title":"Cardiac tamponade: Clinical, etiological and therapeutic features","authors":"Syrine Saidane ,&nbsp;Sana Said ,&nbsp;Younes El Kharras ,&nbsp;Walid Ben Fakih ,&nbsp;Khadija Mzoughi ,&nbsp;Ihsen Zairi ,&nbsp;Sondos Kraiem","doi":"10.1016/j.acvd.2025.03.037","DOIUrl":"10.1016/j.acvd.2025.03.037","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiac tamponade is a life-threatening diagnostic and therapeutic emergency.</div></div><div><h3>Objective</h3><div>The aim of our study was to investigate the clinical, etiological and therapeutic characteristics of patients hospitalized for tamponade.</div></div><div><h3>Method</h3><div>This was a retrospective monocentric study including 40 patients admitted for tamponade to our cardiology department between January 2018 and June 2023.</div></div><div><h3>Results</h3><div>The mean age was of 60<!--> <!-->±<!--> <!-->16 years [17,84] with a sex ratio of 2.3. The mode of onset of symptomatology was progressive in 80% of the cases. Dyspnea was constant. The main findings on physical examination were: muffled heart sounds (98%), polypnea (100%), and tachycardia (78%). Mean arterial pressure was 80 mmHg<!--> <!-->±<!--> <!-->15 [47,110]. Paradoxical pulse was present in 15% of cases (<em>n</em> <!-->=<!--> <!-->6). Arterial hypotension was present in 28% (<em>n</em> <!-->=<!--> <!-->11). Signs of right heart failure were present in 11 patients (28%). The main electrical abnormalities reported were: microvoltation (83%), atrial fibrillation (18%) and electrical alternation (30%). Transthoracic echocardiography revealed circumferential effusion in all patients. A “swinging heart” appearance was found in 30% of the cases (<em>n</em> <!-->=<!--> <!-->12). All patients had signs of hemodynamic compression. Thirty-six patients (90%) were drained percutaneously. Surgical drainage was performed immediately in 4 patients and secondarily in only 1 patient whose pericardial puncture was complicated by a right ventricle wound. Neoplastic origin was the main etiology and was found in 14 patients (35%). All cases were secondary neoplasia, and the primary tumor was mainly bronchopulmonary cancer (10 cases) (<span><span>Figure 1</span></span>). Viral origin was the second most common etiology, found in 25% of cases. Other etiologies were iatrogenic (20%), idiopathic (7%), uremic (5%), tuberculosis (5%) and bacterial (3%). The average hospital stay was 8<!--> <!-->±<!--> <!-->5 days [3,27]. The 30-day mortality rate was 12%. Two patients (5%) had a recurrent event: the first case was a neoplasic tamponade and the second was a viral tamponade. No cases of transition to constriction were reported.</div></div><div><h3>Conclusion</h3><div>Tamponade is a serious pathology requiring urgent and effective management. Prognosis depends on the quality of therapeutic management and the nature of the causative pathology.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S189"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099558","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}

{"title":"ADP-ribosylation in a mouse model of atherosclerosis: A potential novel link between dyslipidemia and inflammation in cardiovascular disease","authors":"Constance Delwarde,&nbsp;Diego Pestana,&nbsp;Taku Kasai,&nbsp;Shio Kuraoka,&nbsp;Yuto Nakamura,&nbsp;Takeshi Okada,&nbsp;Julius Decano,&nbsp;Ge Rile,&nbsp;Andrew Mlynarchik,&nbsp;Katelyn Perez,&nbsp;Alesandra Campedelli,&nbsp;Sarvesh Chelvanambi,&nbsp;Sasha Singh,&nbsp;Elena Aikawa,&nbsp;Masanori Aikawa","doi":"10.1016/j.acvd.2025.03.004","DOIUrl":"10.1016/j.acvd.2025.03.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Inflammation and lipid accumulation are major features of atherosclerosis, a leading cause of death and morbidity worldwide. Our previous study recognized ADP-ribosylation, a post-translational modification, as a novel regulator of macrophage activation. We also have established mass spectrometry-based ADP-ribosylation proteomics. Using this technology, we evaluated the completely uncharacterized role of ADP-ribosylation in atherogenesis.</div><div>Objectif We hypothesized that ADP-ribosylated proteins circulate from liver, accumulate in aorta and promote atherogenesis.</div></div><div><h3>Method</h3><div>We harvested the aorta, liver, and plasma of LDL receptor-deficient (Ldlr-/-) mice that were on a regular chow or high-fat diet for 3 or 6 months (<em>n</em> <!-->=<!--> <!-->40/condition).</div></div><div><h3>Results</h3><div>To increase ADP-ribosyl peptide signals in the aorta, we applied our novel recently optimized ion mobility mass spectrometry strategy to generate ADP-ribosylation proteomics data. We analyzed 160 mice aortas and identified 3 APOA1 and 3 APOE ADP-ribosylated peptides in both the aorta and the liver (<span><span>Fig. 1</span></span> A). In addition, these peptides were differentially abundant in the aorta of HFD-fed mice, compared to controls (i.e, APOA1 ARPALEDLR peptide relative abundance [<span><span>Fig. 1</span></span> B]). Using the same mouse plasma, we then validated the presence of ADP-ribosylated APOA1 and ADP-ribosylated APOE in HDL and chylomicron/VLDL/LDL fractions (Western blot), respectively. This finding indicates that classical apolipoproteins circulate as ADP-ribosylated forms, representing a completely novel class of modified apolipoproteins. Immunohistochemistry confirmed the enrichment of aortic lesions in macrophages and ADP-ribosylation signal (5-fold increase, <em>P</em> <!-->=<!--> <!-->0.0006).</div></div><div><h3>Conclusion</h3><div>This work provides the first in vivo evidence that ADP-ribosylation occurs in atherosclerotic lesions, which may originate from the liver via circulating blood (<span><span>Fig. 1</span></span>C). Future studies will examine whether ADP-ribosylation of apolipoproteins, specifically APOA1, alters anti-atherogenic functions of HDL.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S172"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099589","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}

{"title":"Cardiovascular risk factors have an impact on the biology of pericytes","authors":"Célia Bourguignon,&nbsp;Virginie Grouthier,&nbsp;Candice Chapouly,&nbsp;Thierry Couffinhal,&nbsp;Marie-Ange Renault","doi":"10.1016/j.acvd.2025.03.020","DOIUrl":"10.1016/j.acvd.2025.03.020","url":null,"abstract":"<div><h3>Introduction</h3><div>Pericytes are critical for capillary health and function; however, whether and how they may contribute to the pathophysiology of cardiovascular diseases is poorly known. Notably, while the detrimental effects of cardiovascular risk factors on endothelial cells have been extensively studied, little is known about their impact on the biology of pericytes.</div></div><div><h3>Objective</h3><div>Our aim was to investigate pericyte homeostasis in the heart and brain of adult mice, after they have been exposed to type 2 diabetes or depleted by 50%.</div></div><div><h3>Method</h3><div>In vivo, to deplete pericytes, we used Pdgfrb-Cre/ERT2; Rosa-DTA mice in which diphtheria toxin expression is specifically induced in mural cells after tamoxifen injections. Type 2 diabetes was induced in C57BL6/J mice by a high fat diet (HFD; 60% of fat) regimen combined with low dose-streptozotocin (STZ) injections. In vitro experiments were performed on primary cultured mouse cardiac pericytes isolated from 7–14 days-old pups.</div></div><div><h3>Results</h3><div>In diabetes, cardiac pericyte density is reduced by 20% in C57BL6/J mice, suggesting compromised pericyte survival or renewal/proliferation is compromised by diabetes. To investigate whether hyperlipidemia and/or hyperglycemia affect these processes, we conducted in vitro and in vivo assays using cultured cardiac pericytes and DTA mice. We first characterized pericyte renewal in normal conditions by depleting 50% of pericytes in mice. Pericyte regeneration in the heart starts on day 4 after depletion and is almost complete by day 21 (pericyte density<!--> <!-->=<!--> <!-->91% of controls). Consistently, cell proliferation, measured by KI67 staining, was observed from day 4 to day 14 post-depletion. Interestingly, pericyte renewal kinetic seems to be organ-specific: brain pericyte regeneration is slower (71% of controls after 28 days). To test the effects of hyperlipidemia and hyperglycemia on proliferation, mice were fed a high-fat diet or treated with STZ before pericyte depletion. Neither condition impaired pericyte proliferation. In vitro, glucose, free fatty acids, or LDL did not affect BrdU incorporation in cultured pericytes. However, hyperlipidemia may reduce pericyte survival, as free fatty acids, notably palmitate and oleate, significantly increased necrosis in vitro.</div></div><div><h3>Conclusion</h3><div>This study indicates that pericytes can undergo extensive remodeling after a stress in adults. Cardiovascular risk factors, such as obesity and diabetes, may impair pericyte survival in the heart suggesting that these cells, known to be critical for microvascular integrity, could contribute to the onset of cardiac diseases.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S180"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099094","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}

{"title":"Contribution of endothelial cells spatial organization in promoting cardiomyocyte maturation in a cardiac microtissue model","authors":"Gabriel Friob,&nbsp;Jean-Sébastien Vartanian-Grimaldi,&nbsp;Pierre Joanne,&nbsp;Onnik Agbulut","doi":"10.1016/j.acvd.2025.03.021","DOIUrl":"10.1016/j.acvd.2025.03.021","url":null,"abstract":"<div><h3>Introduction</h3><div>The need for a better understanding of the pathophysiological mechanisms underlying cardiovascular diseases of genetic origin has led to the progressive use of cardiomyocytes derived from human induced pluripotent stem cells as a model. Despite the structural and functional immaturity of the cardiomyocytes inherent in this model, numerous studies have shown that the use of different cardiac cell types in three-dimensional co-culture allows cardiomyocytes to mature more rapidly. While the addition of other cell types is known to improve the functionality of the cardiac micro-tissue, little is known about the contribution of the spatial organisation of the cells to this improvement.</div></div><div><h3>Objective</h3><div>In line with the study presented at the 2024 edition of the “Printemps de la Cardiologie”, this study focuses on assessing the impact of endothelial cell spatial organization on the function of cardiac micro-tissue and the maturation of the cardiomyocytes that constitute it.</div></div><div><h3>Method</h3><div>A 3D co-culture model, known as a ‘spheroid’, is created using cardiomyocytes derived from induced pluripotent stem cells through the self-aggregation of various cardiac cell types. Spheroids with the same composition (70% cardiomyocytes<!--> <!-->+<!--> <!-->15% cardiac fibroblasts<!--> <!-->+<!--> <!-->15% endothelial cells) but different organisations (endothelial cells homogeneously distributed or concentrated at the centre of the spheroid) are compared. In addition to the assessment of contractility and calcium dynamics already carried out the previous year, an electron microscopy analysis of the ultrastructural organisation and an assessment of cell death by immunohistochemical labelling were carried out to evaluate the cellular integrity of the spheroids. Finally, RNA-Seq analysis is used for an overall analysis of gene expression in each group, which could potentially explain the origin of the differences observed.</div></div><div><h3>Results</h3><div>As shown last year, the amplitude of contraction and calcium kinetics differed between spheroids pre-formed with a core of endothelial cells and those with homogeneous distribution of cells. Analyses using electron microscopy, RNA-seq and immunohistochemistry show that the functional differences are also reflected at cell level, particularly in terms of cell organisation and viability.</div></div><div><h3>Conclusion</h3><div>The development of this model highlights the importance of the role played by cell organisation in improving the maturation of human cardiomyocytes made possible by 3D co-culture of cardiac cells.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S181"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099029","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}

{"title":"Identification of a Nkx2-5 dosage-dependent progenitor cell population contributing to the Purkinje fiber network","authors":"Louise Michel,&nbsp;Gaetano D’Amato,&nbsp;Rachel Sturny,&nbsp;Nicolas Bertrand,&nbsp;Robert Kelly,&nbsp;Lucile Miquerol","doi":"10.1016/j.acvd.2025.03.033","DOIUrl":"10.1016/j.acvd.2025.03.033","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, particularly in developed countries. Notably, approximately 50% of these deaths occur suddenly, often due to ventricular arrhythmias resulting from defects in the Purkinje fiber (PF) network. PFs are crucial for the rapid conduction of electrical impulses through the ventricles, ensuring the synchronized contraction of the heart. Despite their clinical relevance, the molecular mechanisms governing PF development and maturation are not fully understood. Our group has previously shown that PFs arise from embryonic trabecular myocardium, with their commitment to the PF fate being regulated by high levels of the transcription factor Nkx2-5. Genetic deletion of one copy of Nkx2-5 in mice results in a hypoplastic PF network, likely due to defective PF commitment during ventricular morphogenesis.</div></div><div><h3>Objective</h3><div>Building on this model, we aim to define the transcriptional landscape that governs PF commitment and maturation, both under normal and pathological conditions.</div></div><div><h3>Method</h3><div>1) Single cell transcriptomic analysis (scRNA-seq) from embryonic (E)11.5 WT and Nkx2–5<!--> <!-->±<!--> <!-->hearts. 2) Expression pattern and genetic lineage tracing of Lysozyme M (Lyz2), a novel PF marker.</div></div><div><h3>Results</h3><div>ScRNA-seq cluster and DEG analysis identifies a trabecular cardiomyocyte (CM) population expressing high levels of Lyz2 in WT but not Nkx2–5<!--> <!-->±<!--> <!-->E11.5 hearts. Intriguingly, Lyz2 expressing CMs (high Lyz2) co-express a subset of genes required for conductive CM commitment. Time-course lineage tracing analysis using a Lyz2-Cre driver reveals that Lyz2-derived CMs contribute to the VCS in adult WT hearts. In contrast, in Nkx2–5<!--> <!-->±<!--> <!-->hearts, Lyz2-derived cells only minimally contribute to the hypoplastic PF network.</div></div><div><h3>Conclusion</h3><div>Our results identify a progenitor cell population within the developing trabeculae that expresses high levels of Lyz2 and contributes to the formation of the VCS in an Nkx2–5-dependent manner.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S187"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099046","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}

{"title":"Early postnatal overfeeding influence on cardiac composition and metabolism in juvenile mice","authors":"Marie Josse ,&nbsp;Léa Longin ,&nbsp;Eve Rigal ,&nbsp;Nathalie Rosenblatt-Velin ,&nbsp;Francesca Rochais ,&nbsp;Jean-Paul Pais De Barros ,&nbsp;Luc Rochette ,&nbsp;Catherine Vergely","doi":"10.1016/j.acvd.2025.03.113","DOIUrl":"10.1016/j.acvd.2025.03.113","url":null,"abstract":"<div><h3>Introduction</h3><div>Shortly after birth, the cardiac metabolism shifts from anaerobic glycolysis as the main energy source to predominantly relying on fatty acid β-oxidation. Concomitantly, cardiomyocytes lose their ability to proliferate to switch towards a hypertrophic growth, but variations in the availability and utilization of metabolic substrates influences this postnatal proliferative window. Postnatal overfeeding (PNOF) induced by litter size reduction in rodents mimics the effects of childhood over nutrition.</div></div><div><h3>Objective</h3><div>The aim of this study was to investigate postnatal cardiac proliferation and early lipid modifications in PNOF juvenile mice.</div></div><div><h3>Method</h3><div>C57BL/6 male pups were raised in litters adjusted to either 9 or 3 pups to form normally fed (NF) or postnatally overfed (PNOF) group, respectively. Hearts were collected at 7, 10, and 24 days post-birth (PN7, PN10, and PN24, respectively) for immunostaining of the proliferation marker Ki67. Lipidomic analyses were performed using liquid chromatography coupled with mass spectrometry on cardiac tissue and plasma from PN7 pups, as well as on milk from dams nursing PN7 pups. Finally, cardiomyocyte number was evaluated on Malassez counting chamber in PN7 and PN24 hearts.</div></div><div><h3>Results</h3><div>PNOF pups exhibited significantly higher body weight and cardiac mass compared to NF controls at all time points. An increase in total fatty acids (FA), including saturated long-chain FA and sphingomyelin, was observed in the milk of PN7 dams. At PN7, while circulating fatty acids remained unchanged, cardiolipin and fatty acid contents were significantly decreased in the hearts of PNOF pups. Lipid peroxidation products including oxysterols, HODE and HETE, were also reduced in both plasma and cardiac tissue. At PN7, cardiomyocyte proliferation rate was significantly reduced and associated with an increase in cardiomyocyte surface. Finally, at both PN7 and PN24, a reduction of cardiomyocyte number per milligram of tissue was observed in PNOF mice.</div></div><div><h3>Conclusion</h3><div>Shortly after birth, the reduction of litter size induces significant changes in milk lipid composition and, consequently, cardiac and plasma lipid changes in PNOF new-borns. PNOF is also associated with cardiomyocyte proliferation changes and cardiomyocyte hypertrophy. Additional investigations are required to determine whether these lipid and cardiac changes are causally linked and to elucidate the mechanisms underlying their relationship.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S223-S224"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099058","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}