Archives of Cardiovascular Diseases最新文献

{"title":"Distinct Ca2+ handling modulation in a rat model of right hypertrophy and dysfunction in response to mild or severe pulmonary artery constriction","authors":"Pauline Le Gourriérec ,&nbsp;Kristelle El Jekmek ,&nbsp;Angele Boet ,&nbsp;Antoine Beauvais ,&nbsp;David Montani ,&nbsp;Olaf Mercier ,&nbsp;Fabrice Antigny ,&nbsp;Jessica Sabourin","doi":"10.1016/j.acvd.2025.03.071","DOIUrl":"10.1016/j.acvd.2025.03.071","url":null,"abstract":"<div><h3>Introduction</h3><div>Right ventricular (RV) function is the most important prognostic factor for patients with pulmonary hypertension. Chronically increased afterload from any cause results in right ventricular failure (RVF). However, the pathophysiological processes that promote RVF are still understudied.</div></div><div><h3>Objective</h3><div>We assessed the Ca2+ dynamic in RV hypertrophy and dysfunction induced by pulmonary artery banding (PAB) in rats to achieve RV overload without affecting the pulmonary vasculature.</div></div><div><h3>Method</h3><div>Using two different degrees of pulmonary artery constriction (mild or severe), cellular Ca2+ imaging was performed on isolated RV cardiomyocytes at 4 weeks post-PAB and sham-operated rats.</div></div><div><h3>Results</h3><div>Our results show that the mild constriction resulted in maladaptive RV hypertrophy, with chamber dilation and reduced systolic function as assessed by echocardiography. The severe constriction accentuated the RV remodeling by increasing the Fulton index and the RV thickness compared to the mild constriction procedure. However, the RV systolic dysfunction is similar between mild and severe PAB. With Fluo-4/AM-based confocal microscopy, we showed that after 4 weeks of mild pressure overload, RV cardiomyocytes had preserved [Ca2+]i transients amplitude, faster [Ca2+]i transients decay time and preserved sarcoplasmic reticulum (SR) Ca2+ load compared to sham myocytes. This was associated with a decrease in cell shortening. After severe pressure overload, RV myocytes presented larger and shorter [Ca2+]i transients and increased SR Ca2+ load associated with enhanced cell shortening.</div></div><div><h3>Conclusion</h3><div>We reveal differences in RV Ca2+ handling modulation depending on the degree of pulmonary artery constriction. This finding provides a more comprehensive analysis of the Ca2+ dynamic at different stages of RV overload.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S206"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099129","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":"Wireless cardiac device for photopharmacological control of cardiac electrical activity","authors":"Matthias Dereli ,&nbsp;Agnès Hivonnait ,&nbsp;Virginie Aillerie ,&nbsp;Pascal Aumond ,&nbsp;Antoine Persello ,&nbsp;Edith Bigot-Corbel ,&nbsp;Hugo Millet ,&nbsp;Michel De Waard ,&nbsp;Flavien Charpentier ,&nbsp;Jérôme Montnach","doi":"10.1016/j.acvd.2025.03.095","DOIUrl":"10.1016/j.acvd.2025.03.095","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiac arrhythmias affect approximately 5% of the population and are associated with high morbidity and mortality. With the aging of the population, their prevalence is increasing, posing a major health challenge. Treatments for preventing or terminating arrhythmias exist (Antiarrhythmic drugs, Implantable cardioverter-defibrillators, ablation techniques…) but they come with important side effects (pro-arrhythmic effects, systemic toxicity…). Photopharmacology, with its high spatio-temporal resolution, emerged as a promising approach for modulating cardiac electrical activity.</div></div><div><h3>Objective</h3><div>We successfully demonstrated its ability to regulate ion channel activity ex vivo and in vivo using an external illumination source. The objective of this study, to consider further clinical application, is to demonstrate the ability of implantable cardiac device to activate photoactivatable peptides and interfere with cardiac activity.</div></div><div><h3>Method</h3><div>A wireless and battery free cardiac device has been previously developed and designed for rats allowing electrical and optical stimulations. We implanted the device on the right ventricular free wall. A photoactivatable analogue of AaHII, an arrhythmogenic peptide, has been intravenously injected and activated locally thanks to 380<!--> <!-->nm illumination in anesthetized rats.</div></div><div><h3>Results</h3><div>We first successfully refined the surgical procedure and validated their tolerance over one month by analyzing electrical and mechanical parameters on ECG and echocardiography, circulating markers of heart injury and histology. The device is well tolerated over one month without any signs of inflammation or arrhythmias. We next demonstrated that 70% of the device-mediated photoactivations (5/7 rats), leads to a significant change in the electrical activity of the heart characterized by an increase of the T wave area on the ECG. Interestingly, all animals recovered quickly validating the local activation of the peptide.</div></div><div><h3>Conclusion</h3><div>This study is very promising for future applications of photopharmacology, and pave the road for local photoactivation of antiarrhythmic peptides to prevent or terminate arrhythmias in preclinical models.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S218"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099125","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":"Valves in pulmonary veins: New approach for the heterotopic treatment of mitral regurgitation","authors":"Zoubaire Moustaine ,&nbsp;Emma Sulmoni ,&nbsp;Gregory De Crescenzo ,&nbsp;Benoit Liberelle ,&nbsp;Wael Saleh ,&nbsp;Guy Leclerc ,&nbsp;Lyes Kadem ,&nbsp;Anne-Sophie Zenses ,&nbsp;François Tournoux","doi":"10.1016/j.acvd.2025.03.082","DOIUrl":"10.1016/j.acvd.2025.03.082","url":null,"abstract":"<div><h3>Introduction</h3><div>Severe mitral regurgitation (MR) can be surgically addressed when the operative risk is considered acceptable. If not, several percutaneous approaches have been developed, including percutaneous mitral valve replacement and edge-to-edge repair. However, there is still an unmet need for a procedure to manage patients who are too frail for cardiac surgery and for whom current percutaneous options are contraindicated or have failed. We hypothesized that the implantation of percutaneous valves within the pulmonary veins (PV) could protect the patient from the consequences of a severe MR.</div></div><div><h3>Objective</h3><div>To design a synthetic valve that can be implanted in PVs for the heterotopic treatment of severe MR and test its performance in restoring cardiac output (CO) in a phantom model.</div></div><div><h3>Method</h3><div>An innovative process to produce customizable synthetic prosthetic valves was developed: molds of a valve prosthesis designed to be inserted in a PV were 3D-printed and used to produce prostheses made of polyvinyl alcohol hydrogel. Subsequently, in vitro tests have been conducted to evaluate the performance of the prosthetic valves under physiological conditions. The phantom includes 6 main components mimicking a left atrium (LA) with 3 PVs, a 5<!--> <!-->mm diameter orifice as depressurization system (DS), an anatomically correct mitral valve, a dynamic left ventricle, an aortic valve, and an aorta (<span><span>Figure 1</span></span>). The coaptation of the mitral valve leaflets was adjusted to simulate levels of MR. Four different conditions were tested three times each: 1) No MR, no valve in PVs and DS closed (control position); 2) Severe MR, no valve in PVs and DS closed; 3) Severe MR, valves inserted in each PV and DS closed; 4) Severe MR, valves inserted in each PV and DS open to mitigate a rise in LA pressure (LAP). Forward cardiac output (CO) and mean LAP were assessed.</div></div><div><h3>Results</h3><div>In the control condition mimicking a healthy subject, the CO was 3.96<!--> <!-->±<!--> <!-->0.05<!--> <!-->L/min and the mean LAP was 2.8<!--> <!-->±<!--> <!-->1.2<!--> <!-->mmHg. When severe MR was induced (condition 2), the CO dropped to 2.16<!--> <!-->±<!--> <!-->0.16<!--> <!-->L/min and the mean LAP increased to 4.0<!--> <!-->±<!--> <!-->1.1<!--> <!-->mmHg. Once prosthetic valves were added in the PVs (condition 3), the CO rose up to 3.37<!--> <!-->±<!--> <!-->0.33<!--> <!-->L/min and the mean LAP up to 31.7<!--> <!-->±<!--> <!-->1.3<!--> <!-->mmHg. With the DS opening (condition 4), the mean LAP dropped to 22.9<!--> <!-->±<!--> <!-->1.5<!--> <!-->mmHg with a slight reduction in CO (2.98<!--> <!-->±<!--> <!-->0.04<!--> <!-->L/min).</div></div><div><h3>Conclusion</h3><div>This proof-of-concept study successfully demonstrates that implantation of valves in PVs can restore CO in presence of severe MR and that a DS can mitigate the resulting rise in LAP.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S211-S212"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099171","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":"Resveratrol cardioprotection associated with adipose tissue autotaxin pathway inhibition in a diet induced prediabetic female rat model","authors":"Alexis Jouenne ,&nbsp;Joevin Sourdon ,&nbsp;Isabelle Varlet ,&nbsp;Frank Kober ,&nbsp;Jean-François Landrier ,&nbsp;Monique Bernard ,&nbsp;Martine Desrois","doi":"10.1016/j.acvd.2025.03.046","DOIUrl":"10.1016/j.acvd.2025.03.046","url":null,"abstract":"<div><h3>Introduction</h3><div>Prediabetes is associated with an increased cardiovascular risk, but recent data also highlight the importance of the role of the liver and adipose tissue in cardiovascular risk stratification in this context. These inter-organ relationships still require further investigation, as well as finding new therapeutic approaches, especially in women who present a higher cardiovascular risk than men as early as the prediabetes stage.</div></div><div><h3>Objective</h3><div>Here, we evaluated the effects of resveratrol supplementation (RSV) on the heart/adipose tissue axis in prediabetic female rats submitted to high-fat-high-sucrose diet (HFS).</div></div><div><h3>Method</h3><div>30 Female Wistar rats were divided into 3 groups fed for 5 months with: a standard diet (CTRL), HFS diet (HFS) or HFS diet supplemented for the last 2 months with RSV (1<!--> <!-->mg/kg/day in water) (RSV). In vivo Magnetic Resonance Imaging was performed to study cardiac morphology/function. Then, tolerance to ischemia-reperfusion (IR) injury was investigated ex vivo by simultaneous measurement of cardiac function (RPP, EDP) and energy metabolism by 31P Magnetic Resonance Spectroscopy. Finally, the expression of autotaxin (ATX) Enpp2 gene, a protein suggested to be involved in deleterious cardiac remodeling, in perirenal adipose tissue as well as its plasma concentration were measured.</div></div><div><h3>Results</h3><div>HFS diet induced glucose intolerance (<em>P</em> <!-->&lt;<!--> <!-->0.01 vs CTRL), deleterious cardiac remodeling (<em>P</em> <!-->&lt;<!--> <!-->0.05 vs CTRL), but also impaired myocardial IR tolerance, with diminished cardiac function (RPP, EDP) along with reduced ATP and PCr percentages of recovery during reperfusion (<em>P</em> <!-->&lt;<!--> <!-->0.05 vs CTRL). These HFS induced impairments were associated with increased adipose tissue ATX gene relative expression and ATX plasmatic levels (<em>P</em> <!-->&lt;<!--> <!-->0.05 vs CTRL). RSV supplementation ameliorated glucose intolerance (<em>P</em> <!-->&lt;<!--> <!-->0.01 vs HFS), restored deleterious cardiac remodeling (<em>P</em> <!-->&lt;<!--> <!-->0.01 vs HFS) and increased IR tolerance [higher cardiac function and ATP, PCr percentages of recovery during reperfusion (<em>P</em> <!-->&lt;<!--> <!-->0.01 vs HFS)]. Interestingly, these ameliorations were associated with restored adipose tissue ATX gene expression and plasmatic levels (<em>P</em> <!-->&lt;<!--> <!-->0.05 vs HFS).</div></div><div><h3>Conclusion</h3><div>A low dose of resveratrol, administered concurrently to an HFS diet, exerted cardioprotection by deleterious cardiac remodeling inhibition and increased IR tolerance. Interestingly, RSV cardioprotection was associated with the inhibition of autotaxin expression in perirenal adipose tissue and ATX plasmatic levels and suggests a yet unknown action path of RSV.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S193"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099172","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":"TNF-alpha inhibits cAMP-mediated phosphorylation of eNOS at serine-633 in endothelial cells","authors":"Vinod Aera,&nbsp;Delphine Angole,&nbsp;Véronique Leblais,&nbsp;Grégoire Vandecasteele,&nbsp;Boris Manoury","doi":"10.1016/j.acvd.2025.03.027","DOIUrl":"10.1016/j.acvd.2025.03.027","url":null,"abstract":"<div><h3>Introduction</h3><div>Inflammatory mechanisms are recognized as players in the pathophysiology of cardiovascular diseases. High levels of tumor necrosis factor-α (TNF-α) occur in heart failure leading to pleiotropic effects. In blood vessels, the second messenger cyclic-adenosine monophosphate (cAMP) mediates vasodilation, inhibits proliferation and improves barrier function. Also, cAMP participates in nitric oxide (NO) synthesis by promoting protein kinase A (PKA)-mediated phosphorylation of endothelial NO synthase (eNOS) at serine-633 (ser633-eNOS). Vascular dysfunction is a hallmark of heart failure, but how inflammatory cytokines influence vascular cAMP pathways is unclear.</div></div><div><h3>Objective</h3><div>The aim of this study is to examine the influence of TNF-α exposure on the cAMP pathway in endothelial cells.</div></div><div><h3>Method</h3><div>Human coronary artery endothelial cells (HCAEC) were cultured between passages 5 and 7. Sub-confluent HCAEC were exposed to TNF-α (10<!--> <!-->ng/mL) or vehicle. After 24<!--> <!-->h treatment, cells were stimulated for 30<!--> <!-->min with isoprenaline (1<!--> <!-->μM) or combination of forskolin analogue (L-858051, 30<!--> <!-->μM) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX, 300<!--> <!-->μM) in order to stimulate cAMP production, or vehicle. Cells were then harvested in ice-cold lysis buffer and frozen. Cell lysates were processed for immunoblot studies. Signals obtained on phosphorylated sites in eNOS and vasodilator-stimulated phosphoprotein (VASP) were normalized to the respective signal obtained for total protein. Where relevant, protein level was normalized to GAPDH level.</div></div><div><h3>Results</h3><div>In control condition, L-858051 with IBMX stimulated the phosphorylation of ser633-eNOS and ser157-VASP significantly (<em>n</em> <!-->=<!--> <!-->4, <em>P</em> <!-->&lt;<!--> <!-->0.05). Cell exposure to TNF-α induced expression of intercellular adhesion molecule ICAM-1. TNF-α significantly decreased total eNOS expression compared to control condition (<em>P</em> <!-->&lt;<!--> <!-->0.05). Interestingly, TNF-α abolished the effect of L-858051 with IBMX on ser633-eNOS phosphorylation, but did not alter that of ser157-VASP (<em>P</em> <!-->&lt;<!--> <!-->0.05). Isoprenaline had no significant effect on any phosphorylation site.</div></div><div><h3>Conclusion</h3><div>Exposure of HCAEC to TNF-α decreased cAMP-related phosphorylation of eNOS while leaving intact the phosphorylation of VASP, a standard surrogate for PKA activation in vascular cells. Future experiments will investigate whether TNF-α diruspts specific cAMP signaling compartments in endothelial cells, which may participate to vascular dysfunction.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S184"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099193","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":"A comparative early outcome analysis of self-expandable and balloon-expandable valves in the management of dysfunctional right ventricular outflow tracts","authors":"Raymond Haddad ,&nbsp;Rouau Quentin ,&nbsp;Grégoire Albenque ,&nbsp;Cohen Sarah ,&nbsp;Pekin Kaan ,&nbsp;Jelena Radojevic ,&nbsp;Estíbaliz Valdeolmillos ,&nbsp;Guirgis Lisa ,&nbsp;Fournier Emmanuelle ,&nbsp;Belli Emre ,&nbsp;Petit Jerôme ,&nbsp;Batteux Clément ,&nbsp;Hascoët Sébastien","doi":"10.1016/j.acvd.2025.03.079","DOIUrl":"10.1016/j.acvd.2025.03.079","url":null,"abstract":"<div><h3>Introduction</h3><div>Self-expandable valves (SEVs) are emerging alternatives to balloon-expandable valves (BEVs) for transcatheter pulmonary valve replacement (TPVR) in patients with dysfunctional right ventricular outflow tracts (RVOTs), though their safety and efficacy remain underexplored.</div></div><div><h3>Objective</h3><div>To compare patient characteristics and outcomes of SEVs and BEVs in TPVR.</div></div><div><h3>Method</h3><div>Clinical and early follow-up data were prospectively analyzed for 139 patients who underwent TPVI between January 2022 and June 2024 using Edwards SAPIEN 3 (ES3) BEVs or Venus-P SEVs.</div></div><div><h3>Results</h3><div>Cohort: 59.7% male, median weight 65<!--> <!-->kg; 66.2% received ES3 valves (<em>n</em> <!-->=<!--> <!-->92) and 33.8% Venus-P (<em>n</em> <!-->=<!--> <!-->47). Median age was 33.2 years (IQR: 19.7–42.8) for ES3 and 44.7 years (IQR: 32.6–54.1) for Venus-P (<em>P</em> <!-->&lt;<!--> <!-->0.001). Tetralogy of Fallot was the underlying diagnosis in 53.2%. Lesion types included stenosis (13.7%), pulmonary regurgitation (66.9%), and mixed (19.4%). Native RVOTs were present in 5.4% of ES3 and 31.9% of Venus-P cases, while patched RVOTs were found in 41.3% and 68.1%, respectively. Median valve diameter was 36<!--> <!-->mm (IQR: 34–36) for Venus-P and 26<!--> <!-->mm (IQR: 23–29) for ES3 (<em>P</em> <!-->&lt;<!--> <!-->0.001). All implantations were successful. Median fluoroscopy time was 18<!--> <!-->min (IQR: 13–27) for ES3 and 22.6<!--> <!-->min (IQR: 19–26) for Venus-P (<em>P</em> <!-->=<!--> <!-->0.02). Postoperative median RVOT maximum velocity was 2<!--> <!-->m/s (IQR: 1.6–2.5). Valve insufficiency was moderate in 4.3%, mild in 6.5%, and absent in 89.2%. Moderate adverse events occurred in 7.2% (3.3% ES3, 14.9% Venus-P; <em>P</em> <!-->=<!--> <!-->0.01), and ventricular arrhythmias requiring therapy in 9.4% (2.2% ES3, 23.4% Venus-P; <em>P</em> <!-->&lt;<!--> <!-->0.001).</div></div><div><h3>Conclusion</h3><div>SEVs are effective for TPVR but have higher rates of adverse events and ventricular arrhythmias than BEVs, necessitating vigilant long-term follow-up.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S210"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099196","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 neural stem-like cells in adult rodent intrinsic cardiac nervous ganglia","authors":"Alice Jean ,&nbsp;Guénaëlle Lizot ,&nbsp;Mathieu Gourmelon ,&nbsp;Fabrice Antigny ,&nbsp;Laetitia Cousin ,&nbsp;Patricia Arnaud ,&nbsp;Jocelyn Bescond ,&nbsp;Patrick Bois ,&nbsp;Bruno Constantin ,&nbsp;Valérie Coronas ,&nbsp;Aurélien Chatelier","doi":"10.1016/j.acvd.2025.03.059","DOIUrl":"10.1016/j.acvd.2025.03.059","url":null,"abstract":"<div><h3>Introduction</h3><div>At the cardiac level, the intrinsic cardiac nervous system (ICNS) functions as a local integration center for autonomic afferent signals. As such, it plays a critical role in the regulation of cardiac function, and its pathophysiological remodeling is subject to growing research interest. Recent evidence suggests that progenitor cells lead to neurogenesis in the adult peripheral nervous system. This interrogates the potential presence and role of such progenitor cells within the ICNS and their involvement in pathological remodeling.</div></div><div><h3>Objective</h3><div>Given that ICNS can be influenced by cardiac pathologies and clinical interventions such as atrial fibrillation ablation, we investigated the presence of progenitor cells in the adult ICNS and their capacity to exhibit key stem cell properties in vitro.</div></div><div><h3>Method</h3><div>Cardiac ganglia from adult mice were dissociated and cultured in neural stem cell medium. Progenitor cells were identified through the expression of stem cell markers SOX2 and nestin. Self-renewal and proliferative capacities were assessed by replating experiments and by the expression of the Ki-67 marker. In vitro differentiation was evaluated through BrdU incorporation and beta III tubulin expression in differentiation medium. Besides, the impact of a monocrotaline-induced rat model of right heart disease on progenitor cell proliferation was assessed in situ via immunohistochemistry.</div></div><div><h3>Results</h3><div>Our study demonstrated the presence of the stem cell marker SOX2 in the cardiac ganglia of adult mice. In vitro, these cells form primary spheres that express the proliferation marker Ki-67, along with the progenitor markers SOX2 and Nestin. These spheres can be replated to obtain secondary sphere expressing the same markers indicating the self-renewing properties of SOX2 positive cells. Besides, these cells undergo differentiation in culture toward a neuronal fate, as demonstrated by the expression of tubulin beta 3, the neuron specific protease PGP9.5 and PSA-NCAM. Finally, numerous proliferative cells expressing Ki-67 can be observed in ganglia of the monocrotaline rat model compared to control, including SOX2 positive cells.</div></div><div><h3>Conclusion</h3><div>Our study unveils for the first time the existence of neurogenesis in adult rodent ICNS through the identification of SOX2 positive cells that display properties of neuronal progenitor in vitro.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S200-S201"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099341","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":"Involvement of platelet factor 4 in myocardial ischemia/reperfusion","authors":"Simon Chesseron ,&nbsp;Estelle Archer ,&nbsp;Ana Valéria Vinhais Da Silva ,&nbsp;Claire Pouplard ,&nbsp;Caroline Vayne ,&nbsp;Sébastien Roger ,&nbsp;Fabrice Ivanes ,&nbsp;Jérôme Rollin","doi":"10.1016/j.acvd.2025.03.048","DOIUrl":"10.1016/j.acvd.2025.03.048","url":null,"abstract":"<div><h3>Introduction</h3><div>Ischemia/reperfusion injury (IRI) is a key process in the initiation of post-infarction pathological remodeling. Several studies demonstrated that platelets play a major role in the development of IRI due to their abundance at ischemic sites. Platelet activation leads to the secretion of platelet proteins, some of which (TGF-β, PDGF,..) are already involved in pathological ventricular remodeling. Among these, platelet factor 4 (PF4) is the most abundant chemokine and has already been implicated in the development of fibrosis in tissues such as the lung and skin.</div></div><div><h3>Objective</h3><div>To evaluate the role of platelet factor 4 (PF4) in cardiac fibroblasts differentiation and the subsequent development of cardiac fibrosis. Additionally, to determine whether targeting PF4 could serve as an innovative therapeutic strategy using human anti-PF4 monoclonal antibodies developed in our laboratory.</div></div><div><h3>Method</h3><div>First, characterization of the effect of platelet factor 4 on cardiac fibroblasts primary culture by assessing fibrosis markers in normoxia condition or subjected to oxygen and nutrient deprivation stress. For therapeutic purposes, human anti-PF4 monoclonal antibodies previously developed in our laboratory (1E12, 1C12 and 5B9) were used to target the effect of PF4 in the differentiation of fibroblasts into myofibroblasts.</div></div><div><h3>Results</h3><div>Our results show that PF4 (5<!--> <!-->μg/mL) induces a significant increase in α-sma (alpha-smooth muscle actin) expression in cardiac fibroblasts, under normoxic conditions as well as under conditions of nutrient and oxygen deprivation. Treatment of cardiac fibroblasts with a therapeutic concentration of heparin, which can interact with PF4 and is used as first-line therapy in post-infarction patients, had no effect on the PF4-induced increase in α-sma expression. However, anti-PF4 monoclonal antibodies significantly reduced the expression of the fibrosis marker expressed by FP4-induced cardiac fibroblasts.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the role of PF4 in the differentiation of cardiac fibroblasts towards the myofibroblastic profile, which initiates fibrosis. Furthermore, the use of anti-PF4 antibodies decreases PF4-dependent cardiac fibroblast differentiation in normoxia and under conditions of nutrient and oxygen stress, suggesting a potential innovative strategy for targeting fibrosis associated with pathological left ventricular remodeling after myocardial infarction.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S194"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099352","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":"Impact of baseline renal function on long-term outcomes after acute myocardial infarction","authors":"Ameni Mardessi,&nbsp;Sarra Chenik,&nbsp;Houaida Mahfoudhi,&nbsp;Taha Yassine Jabloun,&nbsp;Abdedayem Haggui,&nbsp;Nadhem Hajlaoui,&nbsp;Wafa Fehri","doi":"10.1016/j.acvd.2025.03.052","DOIUrl":"10.1016/j.acvd.2025.03.052","url":null,"abstract":"<div><h3>Introduction</h3><div>The cardiac prognosis, particularly coronary, is overshadowed by the presence of chronic kidney disease, which is increasingly recognized as a major cardiovascular risk factor.</div></div><div><h3>Objective</h3><div>The objective of this study is to demonstrate the involvement of renal function in cardiovascular risk.</div></div><div><h3>Method</h3><div>Our study includes 244 patients admitted to the cardiology department of the main military hospital of Tunis for acute coronary syndrome, divided into two groups: group 1 comprises 188 patients with a glomerular filtration rate (GFR)≥<!--> <!-->60<!--> <!-->mL/min, and group 2 contains 41 patients with GFR<!--> <!-->&lt;<!--> <!-->60<!--> <!-->mL/min.</div></div><div><h3>Results</h3><div>The mean age of patients included in the study is 62.09 years with a male predominance, yielding a sex ratio of 1.65. It's noted that a history of smoking, dyslipidemia, stroke, and/or hypertension is more prevalent among patients with renal insufficiency. Patients with a GFR<!--> <!-->&lt;<!--> <!-->60<!--> <!-->mL/min significantly experienced more cardiovascular events (16.1% in group 2 compared to 5.4% in group 1; <em>P</em> <!-->=<!--> <!-->0.049) with a higher number of subsequent hospitalizations (53.8% had a hospital stay of more than 3 days). In multivariate analysis, renal insufficiency is an independent predictor of cardiovascular events (<em>P</em> <!-->=<!--> <!-->0.05). Among patients with chronic kidney disease, a history of stroke (<em>P</em> <!-->=<!--> <!-->0.037), primary angioplasty (<em>P</em> <!-->=<!--> <!-->0.000), and/or coronary revascularization surgery (<em>P</em> <!-->=<!--> <!-->0.016) were predictive factors of long-term major events.</div></div><div><h3>Conclusion</h3><div>The findings of our study confirm that baseline renal function is a potent predictor of long-term events after myocardial infarction, highlighting the need to include renal function in the assessment of cardiovascular risk and to tailor the management of patients admitted for acute myocardial infarction accordingly.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S196-S197"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099422","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":"CPVT-related arrhythmogenic mechanisms: Ca2+-induced transmural electrophysiological gradient alteration in a RyR2-V2475F rabbit model","authors":"Garance Gérard ,&nbsp;Alvarado Francisco ,&nbsp;Zheng Jingjing ,&nbsp;Valdivia Héctor ,&nbsp;Ana Maria Gomez Garcia ,&nbsp;Jean-Pierre Benitah ,&nbsp;Romain Perrier","doi":"10.1016/j.acvd.2025.03.087","DOIUrl":"10.1016/j.acvd.2025.03.087","url":null,"abstract":"<div><h3>Introduction</h3><div>Inherited stress-induced ventricular arrhythmia, such as catecholaminergic polymorphic ventricular tachycardia (CPVT), is typically linked to excessive diastolic Ca2+ release from the cardiac sarcoplasmic reticulum (SR) via the ryanodine receptor (RyR2), triggering Na+/Ca2+ exchanger activity and delayed afterdepolarizations. However, altered Ca2+ release may also influence sarcolemmal ionic conductance, shaping cardiac electrical properties.</div></div><div><h3>Objective</h3><div>We investigated the impact of the RyR2-V2475F, using a rabbit knock-in model to determine the underlying arrhythmogenic mechanisms of this mutation.</div></div><div><h3>Method</h3><div>Action Potentials (APs) and Ca2+ currents (ICaL) were recorded using patch-clamp on left ventricle cardiomyocytes. Ca2+ sparks, SR Ca2+ load and Ca2+ transients were analyzed using confocal microscopy. Ion channels expression was studied using Western-Blotting.</div></div><div><h3>Results</h3><div>Analysis of intracellular Ca2+ homeostasis revealed that Ca2+ transient amplitude was reduced, correlating with smaller SR Ca2+ load in isolated ventricular RyR2-V2475F± cardiomyocytes compared to WT. This could be dependent on the activity of RyR2, as we found that the SR Ca2+ leak was increased. Nevertheless, the leak was mostly undetectable, as Ca2+ sparks frequency was depressed. These alterations were associated with a reduced window L-type Ca2+ current contributing to SR Ca2+ unloading in RyR2-V2475F± cardiomyocytes. Additionally, we noted a shortening of action potential duration of endocardial cardiomyocytes from RyR2-V2475F± rabbits. The resulting inversion of the transmural repolarization gradient was abolished in the presence of BAPTA, suggestive of a Ca2<!--> <!-->+<!--> <!-->-dependent effect, and could represent a vulnerable substrate that favors the appearance of arrhythmias. Indeed, RyR2-V2475F± rabbits developed a CPVT-like phenotype under pharmacological stress challenge. Interestingly, this phenotype was more pronounced in males than in females, consistent with a lesser impact on APs and ICaL of V2475F± in female animals.</div></div><div><h3>Conclusion</h3><div>Using a rabbit RyR2-V2475F model, we uncovered a potential new mechanism for CPVT-related arrhythmias, defined by a differential impact on AP duration between endocardium and epicardium, leading to a loss of an important protection mechanism against arrhythmias.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S214-S215"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099565","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}