Archives of Cardiovascular Diseases最新文献

{"title":"Role of macrophage efferocytosis receptors in post-ischemic myocardial remodeling","authors":"Alexandra Achab Ali ,&nbsp;Paul Alayrac ,&nbsp;Yanyi Sun ,&nbsp;Mathilde Lemitre ,&nbsp;José Vilar ,&nbsp;Angelique Levoye ,&nbsp;Hamidou Feriel ,&nbsp;Clément Cochain ,&nbsp;Stephane Camus ,&nbsp;Jean-Sébastien Silvestre","doi":"10.1016/j.acvd.2025.03.050","DOIUrl":"10.1016/j.acvd.2025.03.050","url":null,"abstract":"<div><h3>Introduction</h3><div>After acute myocardial infarction (AMI), the massive loss of cardiomyocytes triggers an intense inflammatory response and a progressive adverse remodeling eventually leading to heart failure. Although inflammation is a major determinant of cardiac repair and function in the infarcted heart, it directly fuels pathological remodeling when unchecked. Macrophages (Mps) play an essential role in both inflammatory and reparative phases within the ischemic myocardium and the balance between the two controls disease outcome. Cardiac macrophages populations are heterogenous and encompass embryonically-derived resident cardiac macrophages (RCM) and monocyte-derived macrophages (MDM). RCM possess strong immunomodulatory and reparative functions, largely due to their efferocytosis ability—phagocytosing dead cells to control inflammation and tissue remodeling. RCM are distinguished by high expression of efferocytosis receptors like VSIG4 (V-Set And Immunoglobulin Domain Containing 4) and TIMD4 (T-cell immunoglobulin and mucin domain containing 4). However, the molecular mechanisms linking efferocytosis, macrophage plasticity, and tissue repair remain unclear.</div></div><div><h3>Objective</h3><div>My project aims to investigate the role of VSIG4 and TIMD4 efferocytosis receptors in macrophage-dependent efferocytosis during cardiac repair.</div></div><div><h3>Method</h3><div>Acute MI was induced by permanent ligation of the left anterior descending coronary artery in mice. Cardiac function and remodeling were assessed using echocardiography and immunohistochemistry. Macrophage efferocytosis and impact of efferocytosis on macrophage signaling pathways, secretion and reprogramming is investigated in primary macrophages.</div></div><div><h3>Results</h3><div>Using single cell RNA sequencing, we revealed that VSIG4 characterized a specific subset of RCM in the cardiac tissue (<span><span>Fig. 1</span></span>). VSIG4 deficiency worsen post-ischemic cardiac function and remodeling, which is rescued when VSIG4+ RCM are reintroduced by intramyocardial injection (<span><span>Fig. 2</span></span>). In vitro, VSIG4 and TIMD4 receptors not only seem to confer Mps with increased dead cell binding capacity but also evoke the AKT and AMPK pathways and trigger the secretion of soluble factors (<span><span>Fig. 3</span></span>).</div></div><div><h3>Conclusion</h3><div>In conclusion, our data suggest that TIMD4+ VSIG4+ RMCs are key regulators of post-ischemic cardiac healing, probably through their enhanced efferocytosis capacity but also the contribution of their regulated efferocytosis-stimulated cytokine secretion.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S195-S196"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099354","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":"Epicardial adipose tissue-derived mediators promote atrial endothelial dysfunction through pro-inflammatory cytokines and the AT1R/NADPH Oxidases/SGLT2 pathway","authors":"Walaa Fakih ,&nbsp;Charbel Alhelou ,&nbsp;Ali Mroueh ,&nbsp;Konstancja Grosjean ,&nbsp;Michel Kindo ,&nbsp;Arnaud Mommerot ,&nbsp;Jean-Philippe Mazzucotelli ,&nbsp;Michael-Paul Pieper ,&nbsp;Patrick Ohlmann ,&nbsp;Olivier Morel ,&nbsp;Valérie Schini-Kerth ,&nbsp;Laurence Jesel","doi":"10.1016/j.acvd.2025.03.088","DOIUrl":"10.1016/j.acvd.2025.03.088","url":null,"abstract":"<div><h3>Introduction</h3><div>Epicardial adipose tissue (EAT) is implicated in left atrial dysfunction via paracrine mechanisms, promoting endothelial dysfunction, pro-arrhythmogenic effects, and tissue remodeling, all of which favor the onset of atrial fibrillation (AF). Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have recently been shown to reduce AF incidence, EAT volume, and inflammation, but the underlying mechanisms remain unclear.</div></div><div><h3>Objective</h3><div>This study explores the effects of human EAT-derived mediators on atrial endothelial cell (AEC) function and evaluates the role of SGLT2 inhibition using empagliflozin (EMPA).</div></div><div><h3>Method</h3><div>EAT and subcutaneous adipose tissue (SAT) samples were obtained from 70 cardiac patients at Strasbourg University Hospital. Conditioned media (CM) from these tissues were applied to AECs (24<!--> <!-->h). Tissue histology was assessed using hematoxylin and eosin staining, while protein and mRNA expression, reactive oxygen species (ROS), nitric oxide (NO) production, and pro-inflammatory cytokines levels were analyzed through Western blot, RT-qPCR, fluorescence probes, and ELISA, respectively.</div></div><div><h3>Results</h3><div>Compared to SAT, EAT exhibited greater vascularization, increased infiltration of M1-like macrophages, and higher expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), endothelial cell markers (VCAM-1, eNOS), pro-fibrotic proteins (TGF-β), and pro-oxidant factors (NADPH oxidases NOX-1 and SGLT1/2). These changes correlated with elevated oxidative stress, mitigated by inhibitors targeting NOS, NADPH oxidases, ACE, AT1R, or SGLT2. Notably, SGLT2 and ROS levels in EAT were elevated in AF patients and increased with age. On the other hand, EAT-CM contained significantly higher concentrations of pro-inflammatory cytokines compared to SAT-CM. Exposure of AECs to highly inflamed EAT-CM (top quartile) induced oxidative stress, impaired NO production, upregulated p53 and SGLT2 expression, and triggered NF-κB nuclear translocation, whereas CM from less inflamed EAT didn’t induce these effects. EMPA prevented these effects.</div></div><div><h3>Conclusion</h3><div>In conclusion, EAT exhibits higher in situ expression and release of pro-inflammatory cytokines than SAT, contributing to oxidative stress via the AT1R/NADPH oxidases/SGLT2 pathway. Inflamed EAT-CM induces AEC dysfunction and activates NF-κB through cytokine-mediated oxidative stress and SGLT2 signaling. SGLT2 inhibitors may represent a promising strategy to reduce EAT inflammation and prevent cardiac remodeling and fibrosis.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S215"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099095","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 SERCA3 in calcium signaling mediated by α1-adrenoceptors and potential interaction with the NO pathway in mouse aorta","authors":"Maeliss Toth ,&nbsp;Boris Manoury ,&nbsp;Audrey Varin ,&nbsp;Grégoire Vandecasteele ,&nbsp;Régis Bobe ,&nbsp;Véronique Leblais","doi":"10.1016/j.acvd.2025.03.030","DOIUrl":"10.1016/j.acvd.2025.03.030","url":null,"abstract":"<div><h3>Introduction</h3><div>Regulation of vascular tone is a balance between contraction and relaxation of smooth muscle cells (SMC). Calcium plays a key role in these processes, and the Sarco/Endoplasmic Reticulum Ca2<!--> <!-->±<!--> <!-->ATPases (SERCAs) pumps are crucial to regulate calcium homeostasis. While SERCA2 is the predominant isoform in the vascular system, SERCA3 is also co-localized in both SMC and endothelial cells, raising the question of the specific role of SERCA3 in vascular calcium regulation.</div></div><div><h3>Objective</h3><div>Our objective is to investigate the role of SERCA3-dependent calcium signaling in the regulation of mouse aorta vasomotion.</div></div><div><h3>Method</h3><div>Aortas were collected from wild-type (WT) and SERCA3-deficient (KO) male mice and vascular tone was studied by ex vivo myography. Western blot was used to evaluate protein expression in aorta lysates. Cytosolic calcium levels were studied by epifluorescence microscopy in freshly-isolated aortic SMC loaded with the Fura-2 probe (1<!--> <!-->μM).</div></div><div><h3>Results</h3><div>Deletion of SERCA3 leads to a decrease in contractile response specifically to α1-adrenoceptor agonist (phenylephrine, PE) without alteration of the α1-adrenoceptor expression. Interestingly, inhibition of eNOS with L-NAME abolishes this difference in PE-induced contraction between WT and KO aorta. In addition, eNOS phosphorylation (S1177) during PE stimulation is higher in KO compared to WT aortas. Overall, this suggests an increase in the NO-dependent inhibitory control of PE response in KO arteries. Furthermore, contribution of intracellular calcium stores and extracellular calcium influx to PE contractile response were investigated. Using a calcium free extracellular solution and calcium channel blockers (verapamil for L-type calcium channels (LTCC) and 2APB for Store-Operated Calcium Entry (SOCE) inhibition, respectively), we propose that the decreased PE-contraction in KO is due to a reduced calcium influx through LTCC and SOCE. This alteration is not associated to changes in LTCC or TRPC5 expression. Finally, we showed that calcium mobilization in response to PE is reduced in freshly-isolated SMC from SERCA3-KO compared to WT aorta.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that in mouse aorta, SERCA3 regulates the α1-adrenergic-dependent contractile function through modulation of calcium influx (by LTTCs and SOCEs) and the endothelial NO-related relaxing pathway.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S185"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099034","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":"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}