Archives of Cardiovascular Diseases最新文献

{"title":"Is early hyper-O-GlcNAcylation alter placental vascularisation and leaded paediatric cardiac hypertrophy?","authors":"Eva Guilloteau,&nbsp;Amandine Vergnaud,&nbsp;Martin Bouaud,&nbsp;Angelique Erraud,&nbsp;Eva Papin,&nbsp;Manon Denis,&nbsp;Nolwenn Tessier,&nbsp;Benjamin Lauzier","doi":"10.1016/j.acvd.2025.03.024","DOIUrl":"10.1016/j.acvd.2025.03.024","url":null,"abstract":"<div><h3>Introduction</h3><div>Hyperglycaemia observed during pre-gestational or gestational diabetes impacts placental and foetal development. O-GlcNAcylation (O-GlcNAc), a post-translational modification increased in diabetes, disrupts signalling pathways involved in angiogenesis and hypoxic stress response, aggravating poor vascularization. In rat neonatal and adult mouse cardiomyocytes, this dysregulation contributes to cardiac hypertrophy by amplifying metabolic stress, inflammation and myocardial remodelling. We postulate that an increase in O-GlcNAc levels associated with maternal hyperglycaemia could be a major determinant in the alteration of placental vascularization and in the development of paediatric cardiac hypertrophy.</div></div><div><h3>Objective</h3><div>This project aims to explore how hyper-O-GlcNAcylation (linked to gestational hyperglycaemia) could affect heart development and induce cardiac pathologies observed in infants delivered from diabetic mothers, and to understand how O-GlcNAc balance modulates placental vasculogenesis and angiogenesis.</div></div><div><h3>Method</h3><div>NButGT (10<!--> <!-->mg/kg) was administered throughout gestation to increase O-GlcNAc level in embryo. Heart and placenta were harvested at 2 different time points: 15.5 and 20.5 embryonic days to evaluate both O-GlcNAc pathway and vasculogenesis and angiogenesis placental and heart (ZO1, VEGF, NO pathway, ROS markers, permeability markers).</div></div><div><h3>Results</h3><div>Treatment with NButGT efficiently increased O-GlcNAc level in heart (E20.5: <em>P</em> <!-->&lt;<!--> <!-->0.0001; E15.5: <em>P</em> <!-->=<!--> <!-->0.0427) and placenta (E20.5: <em>P</em> <!-->=<!--> <!-->0.07). This increase had a strong impact on cardiac (with a loss of weight at E20.5: <em>P</em> <!-->&lt;<!--> <!-->0.02) and placental development as evidenced by a decrease in placental weight (E20.5: <em>P</em> <!-->&lt;<!--> <!-->0.0001). Also, high level of O-GlcNAc levels during development was associated with a modification of the expression of VEGFR2 (decrease) and ZO1 (increase) both in heart (data not shown) and placenta (E15.5: <em>P</em> <!-->&lt;<!--> <!-->0.001; and E15.5: <em>P</em> <!-->=<!--> <!-->0.095; E20.5: <em>P</em> <!-->=<!--> <!-->0.05, respectively).</div></div><div><h3>Conclusion</h3><div>Hyper-O-GlcNAcylation altered foetal development during gestation. Understanding the consequences of hyper-O-GlcNAcylation related to hyperglycaemia during foetal development could significantly advance research and patient treatment, potentially identifying new drug targets.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S182"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099118","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":"Characterization of renal alterations in an experimental model of HFpEF associated with metabolic syndrome in rats","authors":"Umair Sheikh Mohammad ,&nbsp;Géraldine Hubesch ,&nbsp;Grégory Vegh ,&nbsp;Emeline Hupkens ,&nbsp;Pascale Jespers ,&nbsp;Corentin Van Nuffelen ,&nbsp;Singh Sumeet Pal ,&nbsp;Mc Entee Kathleen ,&nbsp;Jean-Luc Vachiéry ,&nbsp;Sandrine Rorive ,&nbsp;Céline Dewachter ,&nbsp;Laurence Dewachter","doi":"10.1016/j.acvd.2025.03.068","DOIUrl":"10.1016/j.acvd.2025.03.068","url":null,"abstract":"<div><h3>Introduction</h3><div>Heart failure with preserved ejection fraction (HFpEF), which now accounts for more than half of all cases of heart failure, is considered to be a major public health problem rising in prevalence due to the ageing of the population and the growing incidence of associated co-morbidities. In patients with HFpEF, renal dysfunction is highly prevalent (up to 50% of patients) and is associated with significant mortality.</div></div><div><h3>Objective</h3><div>To characterize the progression of renal abnormalities in an original experimental model of HFpEF associated with metabolic syndrome in rats.</div></div><div><h3>Method</h3><div>Obesity-prone (OP) and obesity-resistant (OR) rats were fed with a high-fat diet (HFD) or standard chow for 4 and 12 months respectively (10 rats/group). Cardiac function and structure were assessed by echocardiography and heart catheterization, while the kidneys were analyzed at histological and molecular levels. OR rats were used as controls.</div></div><div><h3>Results</h3><div>After 4 and 12 months on a HFD, OP rats developed a metabolic syndrome, which led after 12 months to HFpEF, characterized by left ventricular (LV) diastolic dysfunction, concentric hypertrophy and fibrosis, elevated plasma levels of the cardiac biomarker soluble ST2, together with preserved LV ejection fraction. Renal dysfunction in HFpEF rats was evidenced by increased plasma creatinine and cystatin C levels. Histological analysis showed progressive glomerular enlargement, sclerosis, and tubular inflammation (assessed by MPO staining) at 4 months and worsening at 12 months of HFD. These abnormalities were associated with increased renal expression of kidney injury molecule (Kim)-1 and inflammatory markers, such as intercellular (ICAM) and vascular cell adhesion molecules (VCAM), macrophage marker CD68, and TNF-α, observed at both 4 and 12 months of HFD. Apoptosis (assessed by TUNEL staining) associated with sustained fibrosis (assessed by PicroSirius Red and Masson's trichrome stainings) were observed at both 4 and 12 months of HFD. Circulating pro-inflammatory cytokines, including interleukin (IL)-1β, -6, and -13, were elevated in HFpEF rats.</div></div><div><h3>Conclusion</h3><div>Our results show that renal pathological changes precede the diagnosis of HFpEF. This highlights the complex interplay between cardiac and renal dysfunction in HFpEF, suggesting the need for early clinical intervention targeting both organs.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S205"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099179","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":"Maladaptive arterial wall remodeling in ADPKD patients","authors":"Audrey Dumont ,&nbsp;Caroline Fréguin ,&nbsp;Aurélien Lorthioir ,&nbsp;Michèle Iacob ,&nbsp;Dominique Guerrot ,&nbsp;Jérémy Bellien","doi":"10.1016/j.acvd.2025.03.025","DOIUrl":"10.1016/j.acvd.2025.03.025","url":null,"abstract":"<div><h3>Introduction</h3><div>Autosomal dominant polycystic kidney disease (ADPKD) is a renal hereditary disorder associated with increased cardiovascular mortality, due to mutations in polycystin-1 (PC1) and polycystin-2 (PC2) genes. Experimental evidence suggests that polycystins regulate pressure sensing in vascular smooth muscle cells but this remains to be confirmed in humans.</div></div><div><h3>Objective</h3><div>The objective of this study is to evaluate vascular parameters in patients with autosomal dominant polycystic kidney disease.</div></div><div><h3>Method</h3><div>Carotid artery blood pressures, geometry and function were assessed in 33 non-hypertensive ADPKD patients with preserved renal function and 46 control subjects frequently matched for age, sex and brachial blood pressures, using applanation tonometry coupled with high-resolution echotracking.</div></div><div><h3>Results</h3><div>Compared to controls, ADPKD patients displayed an increase in aortic and carotid systolic and pulse pressures due to altered cardiovascular coupling (<span><span>Fig. 1</span></span>A et 1B). Carotid intima-media thickness (<span><span>Fig. 1</span></span>C) as well as end-diastolic diameter remained unchanged. In addition, aortic and carotid artery stiffness was similar between groups. A genotype/phenotype analysis revealed that, patients with a truncating PKD1 mutation had a lesser intima-media thickness (<span><span>Fig. 2</span></span>A) than patient with a non-truncating PKD1 mutation, despite similar carotid pulse pressure, leading to a marked increase in circumferential wall stress (<span><span>Fig. 2</span></span>B).</div></div><div><h3>Conclusion</h3><div>ADPKD patients exhibit maladaptive arterial remodeling in response to elevated pulse pressure demonstrating the role of polycystins in blood pressure sensing. The paradoxical decrease in arterial wall thickness and associated increase in arterial wall stress in patients with a truncating PKD1 mutation may exacerbate the vascular complications of ADPKD, primarily aneurysms.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S182-S183"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099194","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":"Inflammation and induced-macrophages recruitment in non-syndromic mitral valve dystrophy","authors":"Benjamin Le Vely ,&nbsp;Constance Delwarde ,&nbsp;Claire Toquet ,&nbsp;Pascal Aumond ,&nbsp;Nelli Blank-Stein ,&nbsp;Emilie Charon ,&nbsp;Séverine Remy ,&nbsp;Ignacio Anegon ,&nbsp;Veronika A. Myasoedova ,&nbsp;Vincenza Valerio ,&nbsp;Paolo Poggio ,&nbsp;Solena Le Scouarnec ,&nbsp;Jean-Jacques Schott ,&nbsp;Thierry Le Tourneau ,&nbsp;Elvira Mass ,&nbsp;Jean Mérot ,&nbsp;Romain Capoulade","doi":"10.1016/j.acvd.2025.03.078","DOIUrl":"10.1016/j.acvd.2025.03.078","url":null,"abstract":"<div><h3>Introduction</h3><div>Mitral Valve Prolapse is a common disease affecting 2 to 3% of the population, characterized by a myxomatous mitral valve dystrophy (MVD). Based on the analysis of the FlnA-P637Q KI rat model of non-syndromic MVD, we highlighted that chemotaxis and immune cell migration played a central role in the pathogenesis of MVD, although MVD has been considered so far as a non-inflammatory disease.</div></div><div><h3>Objective</h3><div>To delineate the role of immune cells, specifically macrophages, in MVD pathophysiology.</div></div><div><h3>Method</h3><div>MVD samples from 78 patients with sporadic severe MV regurgitation were sequenced by bulk RNA-seq. KI and WT animals were then studied from birth (D0) to D21 by histology, immunohistology, and flow cytometry to characterize the kinetic of MVD development and the activation/recruitment of macrophages. Bulk RNA-seq was also performed at D7.</div></div><div><h3>Results</h3><div>The transcriptomic analysis of human “end-stage” MVD samples highlighted the activation of signaling pathways related to myxomatous ECM remodeling, valvular cell activation, and TGF-β/BMP, as well as the involvement of leucocyte migration and immune response. Deconvolution algorithm confirmed an enrichment in macrophages. Interestingly, human and D21 rat MVD shared common molecular signature (51% concordance between the top 2000 highly expressed genes), confirming the pertinence of the rat model. Flow cytometry at D21 revealed a 2-fold increase of macrophage in KI MV compared to WT (13% vs 7%, <em>P</em> <!-->&lt;<!--> <!-->0.05). At the early timepoint (D0 and D2), no MVD was detected, although molecular markers of the disease were already overexpressed. At D7, we reported the presence of MVD in KI rats (histological score: 7 vs 4, <em>P</em> <!-->&lt;<!--> <!-->0.001), without increased proportion of macrophages (7% vs 6%, <em>P</em> <!-->=<!--> <!-->0.63). Transcriptomic analysis of D7 MV revealed an enrichment in GO-Terms related to morphogenesis, ECM and cytoskeleton organization, cell activation, as well as a consistent activation of chemotaxis and cytokines activity.</div></div><div><h3>Conclusion</h3><div>This study confirmed a significant contribution of macrophages in the process leading to human MVD. Relying on the sequential analysis of the rat model, we reported a gradual activation of the MVD pathophysiological mechanisms following birth, that further translated to a detectable MVD as early as D7, and in turn lead to the recruitment of macrophages. This study supports the central role of macrophages in the disease development and progression, and open new avenues to develop medical therapy.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S209-S210"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099195","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 impacts of exacerbated emphysema in an elastase-LPS rat model: Effects of emphysema extent and aging","authors":"Yvan Rourre ,&nbsp;Quentin Wynands ,&nbsp;Elodie Desplanche ,&nbsp;Yasmine Colombani ,&nbsp;Roure Charles ,&nbsp;Pierre-Edouard Grillet ,&nbsp;Anne Virsolvy ,&nbsp;Arnaud Bourdin ,&nbsp;Olivier Cazorla","doi":"10.1016/j.acvd.2025.03.063","DOIUrl":"10.1016/j.acvd.2025.03.063","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic Obstructive Pulmonary Disease (COPD), the third leading cause of death worldwide, has two main components: distal airways obstruction and emphysema (destruction of lung parenchyma). This chronic condition is complicated by disease exacerbations, mainly due to infections. COPD patients often present numerous comorbidities, particularly cardiac, which are linked to poor clinical prognosis. Our team previously developed an animal model of exacerbated emphysema: “ELA-LPS” rats, which exhibit heart failure with preserved ejection fraction (HFpEF) 5 weeks after exacerbation, as seen in clinics.</div></div><div><h3>Objective</h3><div>We aimed to determine whether the cardiovascular effects observed in ELA-LPS rats are correlated with the extent of pulmonary emphysema and investigate the influence of aging.</div></div><div><h3>Method</h3><div>Emphysema was induced in male Wistar rats by weekly elastase (ELA) instillations for 4 weeks. The final instillation included bacterial lipopolysaccharide (LPS) to induce exacerbation. In vivo experiments and euthanasia were performed 5 weeks after. Firstly, we tested different doses of elastase (4U, 6U, 10U) in 6-week-old rats to assess whether cardiovascular consequences depend on emphysema severity. Secondly, a dose of 10U elastase was used in 18-month-old rats to study aging effects. Pulmonary emphysema was evaluated by histology and lung compliance was measured ex vivo, while in vivo plethysmography assessed respiratory function. Cardiovascular properties were evaluated in vivo by tail-cuff blood pressure measurement, echocardiography, and maximal cardiorespiratory exercise test (VO2max).</div></div><div><h3>Results</h3><div>In 6-week-old rats, lung histology confirmed elastase dose-dependent emphysema. This led to increased compliance and respiratory dysfunction. ELA-LPS rats exhibited dose-dependent arterial hypertension and HFpEF (preserved LVEF, increased E/E′ ratio), with diastolic dysfunction correlated to emphysema severity (R² <!-->=<!--> <!-->0.53, <em>P</em> <!-->=<!--> <!-->0.0003). These abnormalities resulted in reduced exercise tolerance during VO2max tests. Furthermore, aging worsened impairments, as older rats showed more severe dysfunctions. Notably, old ELA-LPS rats developed heart failure with reduced ejection fraction (HFrEF).</div></div><div><h3>Conclusion</h3><div>Our procedure induced a dose-dependent emphysema with vascular, cardiac (dose-dependent diastolic dysfunction), and general consequences in adult rats. Aging significantly affected the phenotype, with older rats developing HFrEF.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S202"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099202","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":"Differential impact of C57BL/6 substrains on the development of type 1 cardiorenal syndrome","authors":"Raphaël Courcoux ,&nbsp;Rachid Souktani ,&nbsp;Gwladys Berge ,&nbsp;Marie Quétin ,&nbsp;Chloé Samson ,&nbsp;Sandrine Placier-Ouanella ,&nbsp;Juliette Hadchouel ,&nbsp;Marianne Gervais","doi":"10.1016/j.acvd.2025.03.051","DOIUrl":"10.1016/j.acvd.2025.03.051","url":null,"abstract":"<div><h3>Introduction</h3><div>C57BL/6 is one of the most important mouse strains for preclinical research. However, the two main substrains, C57BL/6<!--> <!-->J and C57BL/6<!--> <!-->N have developed over time genetic mutations that could lead to differences in response to pathology. The heart and kidneys are closely linked, and dysfunction of either organ can affect the other, leading to a pathological condition known as cardiorenal syndrome (CRS). Type 1 CRS is characterized by a primary acute cardiac injury, leading to a secondary renal disease. Although some studies have shown differences on the development of acute cardiovascular or renal diseases between these two substrains, the influence of the C57BL/6 background on the development of type 1 CRS remains poorly understood.</div></div><div><h3>Objective</h3><div>The goal of this project is to determine and compare the cardiac and renal outcomes and the development of type 1 CRS after a primary cardiac insult between the two main C57BL/6 substrains.</div></div><div><h3>Method</h3><div>Fourteen weeks old C57BL/6NRj (B6<!--> <!-->N) and C57BL/6JRj (B6<!--> <!-->J) male mice were subjected to permanent coronary artery ligation to generate acute myocardial infarction (MI) or sham surgery. Cardiac and renal functions were analysed by echography and transdermal glomerular filtration rate, 7 and 21 days after the surgery. Cardiac or renal remodeling analysis were performed after 21 days.</div></div><div><h3>Results</h3><div>In both substrains, left ventricular ejection fraction was reduced 21 days after acute MI as compared with their respective sham (<em>P</em> <!-->&lt;<!--> <!-->0.0001). After MI, both substrains significantly developed cardiac hypertrophy, as evidenced by the similar increase of heart weight (+25% in both groups, compared with their respective sham) and cardiomyocyte size (+31% in B6<!--> <!-->J and +18% in B6<!--> <!-->N, compared with their respective sham). Regarding the renal outcome, acute MI resulted in an increase in renal artery pulsatility index (+22% compared with sham), and a decrease in glomerular filtration rate (-20% compared with sham) only in B6<!--> <!-->J mice, whereas both renal parameters remained unchanged in B6<!--> <!-->N background.</div></div><div><h3>Conclusion</h3><div>Overall, our results show that an acute cardiac injury led to the same level of primary cardiac dysfunction in both B6<!--> <!-->J and B6<!--> <!-->N substrains, whereas only the B6<!--> <!-->J develop a secondary kidney disease and a type 1 CRS.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S196"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099421","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":"Peptide-functionalized liposomes for cardiomyocyte targeting","authors":"Alice Boscione ,&nbsp;Rosa Doñate Puertas ,&nbsp;Elias Fattal ,&nbsp;Hervé Hillaireau ,&nbsp;Guillaume Pidoux","doi":"10.1016/j.acvd.2025.03.044","DOIUrl":"10.1016/j.acvd.2025.03.044","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiovascular diseases are the leading cause of death worldwide. While current pharmaceutical therapies are beneficial, they still have several limitations regarding efficacy and side effects. This issue stems from the inadequate targeting of cardiomyocytes and the difficulties that certain therapeutic molecules face in penetrating the intact cell membrane.</div></div><div><h3>Objective</h3><div>We aim to develop a delivery system specifically designed to target cardiomyocytes using liposomes functionalized with our cardiac-targeting peptides. We will evaluate their effectiveness in delivering therapeutic molecules directly to cardiomyocytes in vitro.</div></div><div><h3>Method</h3><div>PEGylated liposomes were produced using the thin lipid film hydration method followed by extrusion. The post-insertion method was used to functionalize the liposomes with various fluorescent labels and peptides. Additionally, direct labeling of liposomes with rhodamine was used to evaluate cellular internalization. Dissociated neonatal rat ventricular cardiomyocytes (NRVM) were incubated for two hours with rhodamine-liposomes to compare three formulations: naked liposomes (LipoRho), liposomes functionalized with the non-specific cell-penetrating peptide TAT (LipoRho<!--> <!-->+<!--> <!-->TAT), and liposomes functionalized with a specific cardiac-homing peptide (LipoRho<!--> <!-->+<!--> <!-->SCHoP) (<span><span>Fig. 1</span></span>).</div></div><div><h3>Results</h3><div>The produced liposomes exhibited a uniform population approximately 140<!--> <!-->nm in size and had a negative surface charge. The optimized post-insertion protocol for functionalizing the liposomes showed an efficiency of about 80% for the SCHoP peptide. Spinning disk confocal images revealed that the liposomes successfully transduced cardiomyocytes. Specifically, LipoRho<!--> <!-->+<!--> <!-->TAT and LipoRho<!--> <!-->+<!--> <!-->SCHoP showed increased internalization in NRVM compared to non-functionalized liposomes (LipoRho).</div></div><div><h3>Conclusion</h3><div>This promising data tackles the unresolved challenge of targeting the heart tissue by demonstrating that a cardiac-targeting peptide can efficiently decorate a liposome surface and enhance its internalization in cardiomyocytes.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S192-S193"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099499","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":"Mitochondrial homeostasis in human aneurysm and dissection of the ascending thoracic aorta","authors":"Alicia Baptista Vicente ,&nbsp;Alexis Richard ,&nbsp;Clara Gourhand ,&nbsp;Maroua Eid ,&nbsp;Linda Grimaud ,&nbsp;Agnès Toutain-Barbelivien ,&nbsp;Bertrand Toutain ,&nbsp;Olivier Fouquet ,&nbsp;Laurent Loufrani","doi":"10.1016/j.acvd.2025.03.016","DOIUrl":"10.1016/j.acvd.2025.03.016","url":null,"abstract":"<div><h3>Introduction</h3><div>Ascending thoracic aortic aneurysms and dissections are fatal pathologies of the aorta. The study of physiopathological mechanisms highlights a medial degeneration characterized by extracellular matrix degradation and smooth muscle cells (SMC) dysregulation. However, pharmacological treatment does not reduce symptoms. Therefore, surgery currently remains the only means to treat aortic aneurysms and dissections. In this context, we focused on the potential roles of mitochondria as predictive factors. Mitochondria adapt their morphology to the physiological and energetic needs of the cell. This process is called mitochondrial dynamics and results from controlled cycles of mitochondrial fission (DRP1, FIS1) and fusion (OPA1, MFN1/2).</div></div><div><h3>Objective</h3><div>Our aim is to study mitochondrial homeostasis in aortic aneurysm and dissection as predictive factors for differentiation or worsening of the pathology.</div></div><div><h3>Method</h3><div>Aortic tissue samples were obtained from a cohort of three patient groups (20/groups): control, aneurysm and dissection. Primary smooth muscle cells were extracted to determine mitochondrial network morphology by confocal microscopy using MitoTracker staining.</div></div><div><h3>Results</h3><div>A decrease in mitochondrial size and shape, as well as in connectivity and mitochondrial network morphology, was observed in patients in the aneurysm group compared with the control and dissection groups. However, no differences in the expression of mitochondrial dynamics proteins were observed. An increase in mitophagy was observed in the aneurysm group, as well as a decrease in ATP synthase and a trend towards a decrease in respiratory chain complexes I and IV in the dissection group. In addition, preliminary results show mitochondrial DNA duplication in the dissection group.</div></div><div><h3>Conclusion</h3><div>These results tend to show differences between the aneurysm and dissection patient groups. These important and innovative results open new avenues of research into potential aggravation factors.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S178-S179"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099090","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 endothelial cells and angiogenesis in cardiomyocyte survival under ischemic stress in a 3D spheroid model","authors":"Jean-Sébastien Vartanian-Grimaldi,&nbsp;Deniz Turques Ceren,&nbsp;Caterina Gargano,&nbsp;Gabriel Friob,&nbsp;Onnik Agbulut","doi":"10.1016/j.acvd.2025.03.019","DOIUrl":"10.1016/j.acvd.2025.03.019","url":null,"abstract":"<div><h3>Introduction</h3><div>Endothelial cells play a crucial role in the function of the majority of tissues in the body, including cardiac tissue. Their ability to regulate angiogenesis, inflammation, and vascular remodeling makes them essential for cardiac tissue homeostasis and repair. Numerous studies support the idea that the inclusion of endothelial cells in 3D cardiac tissue models could significantly enhance cardiomyocyte survival and overall tissue function.</div></div><div><h3>Objective</h3><div>The present study aimed to generate cardiac spheroids using cardiomyocytes and fibroblasts, with or without endothelial cells, to investigate the potential of endothelial cells in protecting cardiac spheroids from ischemic stress.</div></div><div><h3>Method</h3><div>Cardiac spheroid was generated using human primary cardiac fibroblasts, human primary endothelial cells and human cardiomyocytes derived from induced pluripotent stem cells, at a ratio of 1.5:1.5:7, in a spindle-shaped plate. As a control, cardiac spheroid without endothelial cells were also generated. The spheroids were then exposed to an ischemic stress model developed in the laboratory, which combines hypoxia, nutrient deprivation and inflammatory stresses.</div></div><div><h3>Results</h3><div>The spheroids were analyzed 3 days after exposure to ischemic stress. The presence of endothelial cells not only enhanced cardiomyocyte survival, as evidenced by TUNEL staining, but also improved the structural organization of contractile proteins. Furthermore, the presence of endothelial cells in the spheroid protected the contractile function of cardiomyocytes against ischemic stress. Importantly, treatment with the angiogenesis inhibitor, angiostatin, reversed both the functional and structural improvements induced by endothelial cells, highlighting their essential role in preserving cardiomyocyte integrity under stress.</div></div><div><h3>Conclusion</h3><div>In conclusion, the presence of endothelial cells in the cardiac spheroids provides essential structural and functional support to cardiomyocytes. More importantly, our results suggest that the 3D organization of endothelial cells and angiogenesis are key factors driving the observed improvements.</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":"144099093","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":"Characterisation of the role of TTX-sensitive sodium channels (TTX-S Nav) and calcium activated potassium channels (KCa1.1) in cardiac automaticity using huwentoxin-IV and iberiotoxin","authors":"Eliane Morais-Pinto ,&nbsp;Isabelle Bidaud ,&nbsp;Hugo Millet ,&nbsp;Michel De Waard ,&nbsp;Matteo Elia Mangoni ,&nbsp;Jérôme Montnach ,&nbsp;Pietro Mesirca","doi":"10.1016/j.acvd.2025.03.091","DOIUrl":"10.1016/j.acvd.2025.03.091","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiac automaticity is defined by heart capacity to spontaneously generate action potentials (APs) in sino-atrial node mouse cells (SANCs). This capacity is due to diastolic depolarization phase (DD) which is a slow depolarizing phase developing during the diastole of the cardiac contraction cycle. DD is the results of a complex and not yet totally unraveled, interaction between intracellular calcium dynamic and sarcolemma ion channels. Among these ion channels, TTX-sensitive sodium channels (TTX-S Nav) and calcium activated potassium channels (KCa1.1) have been associated with intranodal conduction failure.</div></div><div><h3>Objective</h3><div>To investigate the implication of TTX-S Nav and KCa1.1 ion channels in cardiac automaticity, by using two different natural peptides [huwentoxin-IV (HwTx-IV) and iberiotoxin (IbTx)] inhibiting respectively and selectively these ion channels.</div></div><div><h3>Method</h3><div>SANCs isolated from wild-type mouse were used for ion current and AP recordings using patch-clamp technique. 100<!--> <!-->nM HWTX-IV was perfused on SANCs alone or in combination with 50<!--> <!-->nM TTX (as positive control). ECG intervals were recorded in anesthetised rats in the same conditions to confirm the results in more integrated model. In order to define the right condition to study the effect of KCa1.1 channels in SANCs, HEK cells were transfected with KCa1.1 channels. KCa1.1 current was recorded before and after application of NS 19504 (a KCa1.1 activator) 10<!--> <!-->μM, IbTx 300<!--> <!-->nM and Paxillin 1<!--> <!-->μM.</div></div><div><h3>Results</h3><div>Inhibition of TTX-S Nav channels by 100<!--> <!-->nM HwTx-IV induced a significant reduction of the sodium current which was not enhanced by 50<!--> <!-->nM TTX, a dose knowing to block 100% of TTX-S Nav channels. Moreover, 100<!--> <!-->nM HwTx-IV showed a significant 13% reduction of spontaneous firing frequency in SANCs whereas 50<!--> <!-->nM TTX did not further reduce the SANCs APs rate validating a complete inhibition of TTX-S Nav channels by 100<!--> <!-->nM HwTx-IV. In anesthetised rats, injection of 50<!--> <!-->μg/kg HwTx-IV induced a significant reduction in heart rate without affecting cardiac conduction. In transfected HEK cells, 10<!--> <!-->μM NS doubled KCa1.1 current while 300<!--> <!-->nM IbTx and 1<!--> <!-->μM Paxillin blocked 100% of KCa1.1 current.</div></div><div><h3>Conclusion</h3><div>Inhibition of TTX-S Nav channels significantly reduced spontaneous APs frequency in SANCs, suggesting their important role in cardiac automaticity. IbTx 300<!--> <!-->nM totally blocked KCa1.1 current in HEK transfected cells. Experiments to clarify the role of KCa1.1 channels in cardiac automaticity and crosstalk with TTX-S channels are currently performed.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S216-S217"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099121","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}