Journal of molecular and cellular cardiology plus最新文献

{"title":"New synthetic cannabinoids and the potential for cardiac arrhythmia risk","authors":"Jules C. Hancox ,&nbsp;Caroline S. Copeland ,&nbsp;Stephen C. Harmer ,&nbsp;Graeme Henderson","doi":"10.1016/j.jmccpl.2023.100049","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2023.100049","url":null,"abstract":"<div><p>Synthetic cannabinoid receptor agonists (SCRAs) have been associated with QT interval prolongation. Limited preclinical information on SCRA effects on cardiac electrogenesis results from the rapid emergence of new compounds and restricted research availability. We used two machine-learning-based tools to evaluate seven novel SCRAs' interaction potential with the hERG potassium channel, an important drug antitarget. Five SCRAs were predicted to have the ability to block the hERG channel by both prediction tools; ADB-FUBIATA was predicted to be a strong hERG blocker. ADB-5Br-INACA and ADB-4en-PINACA showed varied predictions. These findings highlight potentially proarrhythmic hERG block by novel SCRAs, necessitating detailed safety evaluations.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"6 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49904642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic research in atherosclerosis: Unravelling plaque phenotype and overcoming methodological challenges","authors":"Miron Sopić ,&nbsp;Kanita Karaduzovic-Hadziabdic ,&nbsp;Dimitris Kardassis ,&nbsp;Lars Maegdefessel ,&nbsp;Fabio Martelli ,&nbsp;Ari Meerson ,&nbsp;Jelena Munjas ,&nbsp;Loredan S. Niculescu ,&nbsp;Monika Stoll ,&nbsp;Paolo Magni ,&nbsp;Yvan Devaux ,&nbsp;CardioRNA COST Action CA17129 and AtheroNET COST Action CA21153","doi":"10.1016/j.jmccpl.2023.100048","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2023.100048","url":null,"abstract":"<div><p>Atherosclerotic disease is a major cause of acute cardiovascular events. A deeper understanding of its underlying mechanisms will allow advancing personalized and patient-centered healthcare. Transcriptomic research has proven to be a powerful tool for unravelling the complex molecular pathways that drive atherosclerosis. However, low reproducibility of research findings and lack of standardization of procedures pose significant challenges in this field. In this review, we discuss how transcriptomic research can help in understanding the different phenotypes of the atherosclerotic plaque that contribute to the development and progression of atherosclerosis. We highlight the methodological challenges that need to be addressed to improve research outputs, and emphasize the importance of research protocols harmonization. We also discuss recent advances in transcriptomic research, including bulk or single-cell sequencing, and their added value in plaque phenotyping. Finally, we explore how integrated multiomics data and machine learning improve understanding of atherosclerosis and provide directions for future research.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"6 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49904645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the neural remodelling landscape in heart failure: A new frontier in cardiac arrhythmogenesis research","authors":"Alexander Grassam-Rowe,&nbsp;Ming Lei","doi":"10.1016/j.jmccpl.2023.100045","DOIUrl":"https://doi.org/10.1016/j.jmccpl.2023.100045","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"5 ","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49859190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific effects of in vitro culture and embryo transfer on cardiac growth in sheep offspring","authors":"Monalisa Padhee ,&nbsp;Mitchell C. Lock ,&nbsp;I. Caroline McMillen ,&nbsp;Song Zhang ,&nbsp;Kimberley J. Botting ,&nbsp;Jens R. Nyengaard ,&nbsp;Severence M. MacLaughlin ,&nbsp;David O. Kleemann ,&nbsp;Simon K. Walker ,&nbsp;Jennifer M. Kelly ,&nbsp;Skye R. Rudiger ,&nbsp;Janna L. Morrison","doi":"10.1016/j.jmccpl.2023.100039","DOIUrl":"10.1016/j.jmccpl.2023.100039","url":null,"abstract":"<div><p>Embryo culture with and without human serum supplementation, previously common practice in assisted reproductive technologies (ARTs), have been associated with increased heart weight in early and late gestation in the sheep fetus. The present study aimed to determine whether the effects of embryo culture and transfer on cardiac growth and associated signalling pathways persist after birth. Embryos were either transferred to an intermediate ewe (ET) or cultured <em>in vitro</em> in the absence (IVC) or presence of human serum (IVCHS) and with methionine supplementation (IVCHS+M) for 6 days after mating. Naturally mated (NM) ewes were used as controls. There was an increase in the number of cardiomyocytes in the left ventricle of IVC and IVCHS+M compared to IVCHS lambs, but only in males. There were no differences in birth weight, body weight, relative heart weight, left ventricular weight, signalling molecules involved in hypertrophy, apoptosis or fibrosis at 6 months of age between the treatment groups. However, there was increased protein abundance of signalling molecules involved in ribosomal biogenesis, in male offspring from the IVC and IVCHS+M groups compared to the IVCHS group. In conclusion, the composition of the culture media used for <em>in vitro</em> embryo culture altered the abundance of proteins involved in ribosomal biogenesis as well as cardiomyocyte endowment in a sex specific manner. Our data suggest that male embryos cultured in the presence of human serum leads to molecular and structural changes that may detrimentally impact cardiovascular health across the life-course.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"5 ","pages":"Article 100039"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44157697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechano-electric feedback mediates the dual effect of stretch in mouse sinoatrial tissue","authors":"Limor Arbel Ganon ,&nbsp;Rami Eid ,&nbsp;Matan Hamra ,&nbsp;Yael Yaniv","doi":"10.1016/j.jmccpl.2023.100042","DOIUrl":"10.1016/j.jmccpl.2023.100042","url":null,"abstract":"<div><p>The sinoatrial node (SAN) is the primary heart pacemaker. The automaticity of SAN pacemaker cells is regulated by an integrated coupled-clock system. The beat interval (BI) of SAN, and its primary initiation location (inferior vs. superior) are determined by mutual entrainment among pacemaker cells and interaction with extrinsic effectors, including increased venous return which stretches the SAN. We aim to understand the mechanisms that link stretch to changes in BI and to heterogeneity of BI in the SAN.</p><p>Isolated SAN tissues of C57BL/6 mice were gradually stretched to different degrees [(low (5–10 % lengthening), medium (10–20 %), and high (20–40 %))] using motor controlled with a custom-made Arduino software. Recordings were acquired 30 s following each level of step. In 8/15 tissues, stretch led to a positive chronotropic response, while in 7/15 tissues, a negative chronotropic response was observed. In the positive chronotropic response group, BI was shortened in parallel to shortening of the local Ca²⁺ release (LCR) period, a readout of the degree of clock coupling. In the negative chronotropic response group, in parallel to a prolongation of BI and LCR period, an unsynchronized firing rate was observed among the cells upon application of stretch. Eliminating the mechano-electrical feedback by addition of blebbistatin disabled the stretch-induced chronotropic effect. Reduction of the sarcoplasmic reticulum Ca²⁺ levels, which mediates the mechano-electrical feedback, by addition of cyclopiazonic acid disabled the dual effect of stretch on SAN function and BI heterogeneity. Thus, the mechano-electric feedback mediates the dual effect of stretch in mouse SAN tissue.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"5 ","pages":"Article 100042"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44109574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KairoSight-3.0: A validated optical mapping software to characterize cardiac electrophysiology, excitation-contraction coupling, and alternans","authors":"Kazi T. Haq ,&nbsp;Anysja Roberts ,&nbsp;Fiona Berk ,&nbsp;Samuel Allen ,&nbsp;Luther M. Swift ,&nbsp;Nikki Gillum Posnack","doi":"10.1016/j.jmccpl.2023.100043","DOIUrl":"10.1016/j.jmccpl.2023.100043","url":null,"abstract":"<div><h3>Background</h3><p>Cardiac optical mapping is an imaging technique that measures fluorescent signals across a cardiac preparation. Dual optical imaging of voltage-sensitive and calcium-sensitive probes allows for simultaneous recordings of cardiac action potentials and intracellular calcium transients with high spatiotemporal resolution. The analysis of these complex optical datasets is both time intensive and technically challenging; as such, we have developed a software package for semi-automated image processing and analysis. Herein, we report an updated version of our software package (<em>KairoSight-3.0</em>) with features to enhance the characterization of cardiac parameters using optical signals.</p></div><div><h3>Methods</h3><p>To test software validity and applicability, we used Langendorff-perfused heart preparations to record transmembrane voltage and intracellular calcium signals from the epicardial surface. Isolated hearts from guinea pigs and rats were loaded with a potentiometric dye (RH237) and/or calcium indicator dye (Rhod-2AM) and fluorescent signals were acquired. We used Python 3.8.5 programming language to develop the <em>KairoSight-3.0</em> software. Cardiac maps were validated with a user-specified manual mapping approach.</p></div><div><h3>Results</h3><p>Manual maps of action potential duration (30 or 80 % repolarization), calcium transient duration (30 or 80 % reuptake), action potential and calcium transient alternans were constituted to validate the accuracy of software-generated maps. Manual and software maps had high accuracy, with &gt;97 % of manual and software values falling within 10 ms of each other and &gt;75 % within 5 ms for action potential duration and calcium transient duration measurements (<em>n</em> = 1000–2000 pixels). Further, our software package includes additional measurement tools to analyze signal-to-noise ratio, conduction velocity, action potential and calcium transient alternans, and action potential-calcium transient coupling time to produce physiologically meaningful optical maps.</p></div><div><h3>Conclusions</h3><p><em>KairoSight-3.0</em> has enhanced capabilities to perform measurements of cardiac electrophysiology, calcium handling, alternans, and the excitation-contraction coupling with satisfactory accuracy.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"5 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/68/nihms-1931538.PMC10544851.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myosin activator omecamtiv mecarbil exhibits divergent inotropic and lusitropic effects in cardiac slices from patients with heart failure","authors":"Fahimeh Varzideh ,&nbsp;Pasquale Mone ,&nbsp;Luigi Salemme ,&nbsp;Imma Forzano ,&nbsp;Angelo Cioppa ,&nbsp;Tullio Tesorio ,&nbsp;Gaetano Santulli","doi":"10.1016/j.jmccpl.2023.100041","DOIUrl":"10.1016/j.jmccpl.2023.100041","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"5 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47366905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omecamtiv mecarbil in precision-cut living heart failure slices: A story of a double-edged sword","authors":"Jorik H. Amesz ,&nbsp;Sanne J.J. Langmuur ,&nbsp;Mark F.A. Bierhuizen ,&nbsp;Natasja M.S. de Groot ,&nbsp;Olivier C. Manintveld ,&nbsp;Yannick J.H.J. Taverne","doi":"10.1016/j.jmccpl.2023.100040","DOIUrl":"10.1016/j.jmccpl.2023.100040","url":null,"abstract":"<div><p>Heart failure (HF) is a rapidly growing pandemic while medical treatment options remain limited. Omecamtiv mecarbil (OM) is a novel HF drug that directly targets the myosin heads of the cardiac muscle. This study used living myocardial slices (LMS) from patients with HF to evaluate the direct biomechanical effects of OM as compared to dobutamine. LMS were produced from patients with end-stage HF undergoing cardiac transplantation or left ventricular assist device implantation and cultured under electromechanical stimulation (diastolic preload: ca. 1 mN, stimulation frequency: 0.5 Hz). Dobutamine and omecamtiv mecarbil (OM) were administered on consecutive days and biomechanical effects were continuously recorded with dedicated force transducers. OM and dobutamine significantly increased contractile force to a similar maximum force, but OM also increased median time-to-peak with 48 % (<em>p</em> = 0.046) and time-to-relaxation with 68 % (<em>p</em> = 0.045). OM administration led to impaired relaxation of HF LMS with increasing stimulation frequencies, which was not observed with dobutamine. Furthermore, the functional refractory period was significantly shorter after administration of OM compared to dobutamine (235 ms (200–265) vs. 270 ms (259–283), <em>p</em> = 0.035). In conclusion, OM increased contractile force and systolic duration of HF LMS, indicating an improvement in cardiac function and normalization of systolic time intervals in patients with HF. Conversely, OM slowed relaxation, which could lead to diastolic filling abnormalities. As such, OM showed benefits on systolic function on one hand but potential hindrances of diastolic function on the other hand.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"5 ","pages":"Article 100040"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45675538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autonomic neuro-cardiac profile of electrical, structural and neuronal remodeling in myocardial infarction-induced heart failure","authors":"Shui Hao Chin ,&nbsp;Emily Allen ,&nbsp;Kieran E. Brack ,&nbsp;G. André Ng","doi":"10.1016/j.jmccpl.2023.100044","DOIUrl":"10.1016/j.jmccpl.2023.100044","url":null,"abstract":"<div><h3>Aims</h3><p>Heart failure is a clinical syndrome typified by abnormal autonomic tone, impaired ventricular function, and increased arrhythmic vulnerability. This study aims to examine electrophysiological, structural and neuronal remodeling following myocardial infarction in a rabbit heart failure model to establish its neuro-cardiac profile.</p></div><div><h3>Methods and results</h3><p>Weight-matched adult male New Zealand White rabbits (3.2 ± 0.1 kg, <em>n</em> = 25) were randomized to have coronary ligation surgeries (HF group, <em>n</em> = 13) or sham procedures (SHM group, <em>n</em> = 12). Transthoracic echocardiography was performed six weeks post-operatively. On week 8, dual-innervated Langendorff-perfused heart preparations were set up for terminal experiments. Seventeen hearts (HF group, <em>n</em> = 10) underwent ex-vivo cardiac MRI. Twenty-two hearts (HF group, <em>n</em> = 7) were examined histologically. Electrical remodeling and abnormal autonomic profile were evident in HF rabbits with exaggerated sympathetic and attenuated vagal effect on ventricular fibrillation threshold, ventricular refractoriness and restitution curves, in addition to increased spatial restitution dispersion. Histologically, there was significant neuronal enlargement at the heart hila and conus arteriosus in HF. Structural remodeling was characterized by quantifiable myocardial scarring, enlarged left ventricles, altered ventricular geometry and impaired contractility.</p></div><div><h3>Conclusion</h3><p>In an infarct-induced rabbit heart failure model, extensive structural, neuronal and electrophysiological remodeling in conjunction with abnormal autonomic profile provide substrates for ventricular arrhythmias.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"5 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/53/main.PMC10512199.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic deletion of 12/15 lipoxygenase delays vascular remodeling and limits cardiorenal dysfunction after pressure overload","authors":"Dae Hyun Lee ,&nbsp;Vasundhara Kain ,&nbsp;Da-Zhi Wang ,&nbsp;Donald G. Rokosh ,&nbsp;Sumanth D. Prabhu ,&nbsp;Ganesh V. Halade","doi":"10.1016/j.jmccpl.2023.100046","DOIUrl":"10.1016/j.jmccpl.2023.100046","url":null,"abstract":"<div><p>The lipid metabolizing enzyme 12/15 lipoxygenase (12/15LOX) induces proinflammatory responses that may increase cardiovascular and renal complications after cardiac insult. To define the role of 12/15LOX, 8–12-week-old male C57BL/6J wild-type (WT; <em>n</em> = 49) and 12/15LOX^−/− mice (<em>n</em> = 50) were subject to transverse aortic constriction (TAC) and monitored for 7, 28, and 56 days (d) post-TAC. Compared with WT, 12/15LOX^−/− mice experienced less left ventricle (LV) dysfunction with limited LV hypertrophy and lung edema post-TAC. 12/15LOX deletion decreased TAC-induced proinflammatory mediators 12-HETE and prostaglandins with modulation in mir-7a-5p, mir 26a-5p, miR-21e-5p, and miR-107-3p during chronic remodeling period (after d28). At d7 post-TAC, 12/15LOX^−/− mice showed increased cardiac gene expression of <em>Arg-1</em> and the prostanoid receptors <em>EP2</em> and <em>EP4</em>. The <em>EP4</em> receptor expression was consistently elevated from d7 till d56 in 12/15LOX^−/− mice post-TAC compared with WT controls. Post-TAC, wheat germ agglutinin staining revealed less cardiomyocyte hypertrophy at d28 and d56 in 12/15LOX^−/− mice compared with WT. TAC-induced vascular remodeling was marked by disruption in the endothelium, evident by irregular CD31 staining and increased alpha-smooth muscle actin (α-SMA) in WT mice at d28 and d56. Compared to WT, 12/15LOX^−/− mice exhibited a diminished expression of NGAL in the kidney, suggesting that 12/15LOX^−/− reduced cardiorenal dysfunction post-TAC. In WT-TAC mice, structural analyses of the kidney revealed glomerular swelling during the maladaptive phase of heart failure, with decreases in the capsula glomeruli space and glomerular sclerosis compared to 12/15LOX^−/− mice. Overall, vascular and kidney inflammation markers were higher in WT than in 12/15LOX^−/− post-TAC. Thus, deletion of 12/15LOX limits LV hypertrophy associated with perivascular inflammation and cardiorenal remodeling after pressure overload. Deficiency of 12/15 LOX serves a dual role in delaying an early adaptive interstitial remodeling with long-term protective effects on cardiac hypertrophy and cardiac fibrosis and detrimental adverse vascular remodeling during later maladaptive remodeling after pressure overload.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"5 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47564091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}