Journal of molecular and cellular cardiology plus最新文献

{"title":"Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression","authors":"Kayla M. Henry ,&nbsp;Richard N. Gardner ,&nbsp;Alexis M. Oppman ,&nbsp;Nastaran Daneshgar ,&nbsp;Mariela Rosales ,&nbsp;Ines Martins ,&nbsp;Kedryn K. Baskin ,&nbsp;Chad E. Grueter","doi":"10.1016/j.jmccpl.2025.100481","DOIUrl":"10.1016/j.jmccpl.2025.100481","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have linked mutations in the Mediator complex, specifically Mediator 13 (Med13) and Mediator 13-like (Med13L), with both congenital heart defects and cardiovascular diseases. Med13 and Med13L are mutually exclusive paralogs within the kinase submodule of the Mediator complex that have been shown to have partially redundant functions in embryonic development and transcription, but their combined roles have not been investigated in the adult heart. We investigated the critical yet redundant roles of Med13 and Med13L in adult murine cardiomyocytes for basal cardiac function.</div></div><div><h3>Methods</h3><div>We generated an inducible Med13 and Med13L cardiomyocyte-specific knockout mouse model to investigate Med13 and Med13L regulation of cardiac function and transcription. We performed RNAseq on mice four weeks after the start of tamoxifen to identify changes in gene expression. Differentially expressed genes were compared across cardiac knockouts of Med13/13L, Med13, Med12, Med1, and Med30 elucidating similar mechanisms of cardiac dysfunction.</div></div><div><h3>Results</h3><div>Med13/13L knockout resulted in decreased cardiac function leading to lethal heart failure in a median timeframe of 6 weeks from the start of tamoxifen. There is significant gene dysregulation after Med13/13L knockout with similar gene dysregulation of fibrotic pathways and calcium handling across Mediator cardiac knockouts.</div></div><div><h3>Conclusions</h3><div>Med13 and Med13L function partially redundantly within the heart to maintain basal cardiac function and transcription, as well as redundancies within cardiac phenotypes related to mediator complex disruptions.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100481"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010208","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 human electromechanical multiscale in-silico models for virtual therapy evaluation","authors":"Maxx Holmes ,&nbsp;Zhinuo Jenny Wang ,&nbsp;Ruben Doste ,&nbsp;Julia Camps ,&nbsp;Hector Martinez-Navarro ,&nbsp;Hannah Smith ,&nbsp;Jakub Tomek ,&nbsp;Blanca Rodriguez","doi":"10.1016/j.jmccpl.2025.100479","DOIUrl":"10.1016/j.jmccpl.2025.100479","url":null,"abstract":"<div><h3>Background</h3><div>Women are under-represented in cardiovascular research, leading to poorer outcomes. Investigating sex-differences in electromechanical function is essential for improving therapy evaluation. This study presents sex-specific human cellular and biventricular electromechanical models for mechanistic investigation of sex-differences in therapeutic response.</div></div><div><h3>Methods</h3><div>Protein genomic expression data from healthy human myocytes calibrated sex-specific electrophysiological models, integrated into biventricular models with male and female anatomies. Multi-scale validation utilised sex-specific clinical and experimental datasets, including responses to drug action. Ionic mechanisms underlying sex-differences in drug response were explored.</div></div><div><h3>Results</h3><div>Simulations showed agreement with clinical ECGs, including QTc intervals (Male: 312 ms; Female: 339 ms), and T-wave amplitude (6–9 % difference). Mechanical biomarkers (LVEF, Female: 68 %; Male: 50 %) matched sex-stratified UK Biobank data (<em>n</em> = 806; 46 % Male). ECG sex-characteristics were driven by ionic differences, while mechanical differences stemmed from anatomical and ionic differences. Simulations predicted exacerbated QTc prolongation under Dofetilide in women (54–78 % higher than males) and T-wave amplitude reduction in men (max: −0.25 mV). Verapamil increased T-wave amplitude in females and decreased it in males, without affecting QTc. Simulations demonstrated reduced repolarisation reserve and increased QTc susceptibility in women via hERG inhibition, while enhanced calcium buffering protected against T-wave amplitude loss. LVEF changes in response to calcium block were more sensitive to anatomical differences between male and female than to ionic sex phenotypes.</div></div><div><h3>Conclusion</h3><div>Sex differences in repolarisation reserve, calcium handling, and anatomy are key factors underpinning ECG and LVEF responses to drugs. Specifically, under calcium block, females showed more preserved LVEF, while under hERG block, females showed more QTc prolongation.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100479"},"PeriodicalIF":2.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843007","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":"Generation and evaluation of a novel PI3K-targeting gene therapy in the failing mouse heart and healthy sheep heart","authors":"Sebastian Bass-Stringer ,&nbsp;Daniel G. Donner ,&nbsp;Clive N. May ,&nbsp;Aya Matsumoto ,&nbsp;Emma I. Masterman ,&nbsp;Aascha A. D'Elia ,&nbsp;Yi Ching Chen ,&nbsp;Helen Kiriazis ,&nbsp;Jieting Luo ,&nbsp;Roger Chooi ,&nbsp;Clara Liu Chung Ming ,&nbsp;Paul Gregorevic ,&nbsp;Colleen J. Thomas ,&nbsp;Bianca C. Bernardo ,&nbsp;Kate L. Weeks ,&nbsp;Julie R. McMullen","doi":"10.1016/j.jmccpl.2025.100478","DOIUrl":"10.1016/j.jmccpl.2025.100478","url":null,"abstract":"<div><div>Heart failure (HF) remains a clinical challenge with cardiac dysfunction typically progressing even with treatment, and heart transplants only available to small numbers. We previously identified phosphoinositide 3-kinase (PI3K, p110α) as a master regulator of exercise-induced cardioprotection, and showed that gene therapy, incorporating a constitutively active form of PI3K (caPI3K) improved function of the failing mouse heart. However, this approach was not cardiac-specific and the gene therapy was challenging to manufacture. The aim of this study was to develop new PI3K-based gene therapies with more optimal properties for clinical translation. We generated and assessed adeno-associated viruses (AAV6) encoding various PI3K constructs, with different enhancers, promoters and transgene components in healthy adult male mice. The most promising AAV construct based on AAV expression, cardiac-specificity, and ease of manufacture contained a cardiac troponin T (cTnT) promoter together with a small region of the regulatory subunit of PI3K (iSH2), and an intron from the β-globin gene which enhances transcription (IVS2). This AAV (1 × 10¹², 2 × 10¹² vg) was administered to mice with myocardial ischemia/reperfusion injury (I/R: 1 h ischemia with reperfusion; AAV delivered 24 h post-I/R). Direct cardiac injections of PI3K-based AAVs were also performed in healthy adult female sheep. I/R mouse hearts treated with the AAV6-cTnT-IVS2-iSH2 displayed increased phosphorylation of Akt, but no improvement in cardiac function or structure was observed. AAV6-cTnT-IVS2-iSH2 successfully transduced healthy sheep hearts which increased endogenous PI3K catalytic activity. Further testing/optimization of the AAV (time of delivery and/or duration) will be required to assess the therapeutic potential of this approach.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100478"},"PeriodicalIF":2.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780892","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":"Current status and challenges of multi-omics research using animal models of atherosclerosis","authors":"Tijana Mitić ,&nbsp;Adriana Georgescu ,&nbsp;Nicoleta Alexandru-Moise ,&nbsp;Michael J. Davies ,&nbsp;Cecile Vindis ,&nbsp;Susana Novella ,&nbsp;Eva Gerdts ,&nbsp;Georgios Kararigas ,&nbsp;Stephanie Bezzina Wettinger ,&nbsp;Melissa M. Formosa ,&nbsp;Brenda R. Kwak ,&nbsp;Filippo Molica ,&nbsp;Nuria Amigo ,&nbsp;Andrea Caporali ,&nbsp;Fernando de la Cuesta ,&nbsp;Ignacio Fernando Hall ,&nbsp;Angeliki Chroni ,&nbsp;Fabio Martelli ,&nbsp;Johannes A. Schmid ,&nbsp;Paolo Magni ,&nbsp;Dimitris Kardassis","doi":"10.1016/j.jmccpl.2025.100476","DOIUrl":"10.1016/j.jmccpl.2025.100476","url":null,"abstract":"<div><div>Atherosclerosis is an underlying cause of cardiovascular diseases (CVD) which account for most deaths worldwide. Use of diverse preclinical models of atherosclerosis has been implemental in understanding the underlying mechanisms, the implicated cell types, the genes and the molecules at play in the onset and progression of atherosclerotic plaques. Although significant research advancements have been made, further research is necessary to delve into factors influencing plaque types, site preference within the vasculature, interactions with adjacent tissues (liver, pancreas and perivascular adipose tissue), inflammation and sex-based disparities, among others. The conventional low throughput methodologies which concentrate on individual cells, genes or metabolites are inadequate to tackle the complex and heterogeneous nature of atherosclerosis. With recent advancement in multi-omics and bioinformatics, research approaches have illuminated a clearer understanding of atherosclerosis. Consequently, these advancements pave the path to design novel therapeutics to complement currently approved lipid-lowering and other effective treatments. In this article, we summarize and critically evaluate the findings derived from recent high throughput single- or multi-omic studies conducted in animal models of atherosclerosis. We also delve into the challenges associated with using experimental animals to model human atherosclerosis and contemplate the essential enhancements needed to better mimic human conditions. We further discuss the requirement of establishing a structured multi-omic database for atherosclerosis research, enabling broader access and utilisation within the scientific community.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100476"},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654739","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":"Cardiology's best friend: Using naturally occurring disease in dogs to understand heart disease in humans","authors":"W. Glen Pyle","doi":"10.1016/j.jmccpl.2025.100474","DOIUrl":"10.1016/j.jmccpl.2025.100474","url":null,"abstract":"<div><div>Heart diseases are a leading cause of death globally. Laboratory and preclinical animal models of disease have been critical in advancing our understanding of the mechanisms of pathology, creating diagnostic tools, and developing therapeutic interventions. However, fundamental biological dissimilarities between humans and rodents limits their usefulness in research, and the induction of disease in an otherwise healthy animal creates unrealistic conditions under which diseases are typically studied. Dogs are at high risk of acquiring and dying from several naturally occurring heart disorders that also affect people. The spontaneous nature of these conditions, along with highly similar cardiovascular systems, offers unique opportunities to investigate cardiovascular disease in a more relevant model for humans. This review focuses on three common cardiac conditions that impact humans and dogs: dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and mitral valve disease – comparing mechanisms of disease, diagnostics, and treatments, to identify strengths and present limitations of their utility. It is noted that the benefits of this research are bidirectional, with the potential to translate knowledge and clinical tools used in veterinary medicine to human patients, and vice versa.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100474"},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570425","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":"Myocardial damage post short-term self-administration cocaine usage in rat","authors":"Muhammad Zubair Saleem ,&nbsp;Tian Liu ,&nbsp;Ningjing Song ,&nbsp;Jayme McReynolds ,&nbsp;Chen Gao","doi":"10.1016/j.jmccpl.2025.100475","DOIUrl":"10.1016/j.jmccpl.2025.100475","url":null,"abstract":"<div><div>Cocaine abuse remains a significant risk with profound adverse impact on cardiovascular health. While long-term cocaine addiction-induced cardiotoxicity is well-documented, the underlying mechanism and the molecular effects of short-term recreational usage of cocaine on the heart have not been well studied. We established a short-term cocaine exposure rat model through self-administration, mimicking real-world recreational cocaine usage. Our results indicate that even such short-term cocaine usage induces deleterious effect on the heart including pathological remodeling and transcriptome reprogramming associated with major metabolic and contractile processes. This study sheds important insight on the molecular mechanisms of short-term exposure of cocaine-induced cardiovascular damage.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100475"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563947","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":"MitoQ Protects Against Oxidative Stress-Induced Mitochondrial Dysregulation in Human Cardiomyocytes","authors":"Alex M. Parker ,&nbsp;Jarmon G. Lees ,&nbsp;Mitchel Tate ,&nbsp;Ren J. Phang ,&nbsp;Anida Velagic ,&nbsp;Minh Deo ,&nbsp;Tayla Bishop ,&nbsp;Thomas Krieg ,&nbsp;Michael P. Murphy ,&nbsp;Shiang Y. Lim ,&nbsp;Miles J. De Blasio ,&nbsp;Rebecca H. Ritchie","doi":"10.1016/j.jmccpl.2025.100469","DOIUrl":"10.1016/j.jmccpl.2025.100469","url":null,"abstract":"<div><div>The overproduction of reactive oxygen species (ROS) and mitochondrial dysregulation are regarded as key mechanisms in the progression of cardiac remodelling in cardiometabolic diseases including heart failure. Conventional treatments are often ineffective as they do not specifically target the underlying pathological mechanisms. Mitoquinone mesylate (MitoQ), a mitochondrial-targeted antioxidant has been reported to be protective against vascular dysfunction in hypertension, diabetic kidney disease and alcohol-induced liver damage. However, the cardioprotective potential of MitoQ to limit oxidative stress-induced mitochondrial remodelling in cardiomyocytes has not been fully resolved. We sought to investigate the effect of MitoQ and its mitochondrial-targeting moiety dodecyl-triphenylphosphonium (dTPP) on hydrogen peroxide-induced overproduction of ROS, mitochondrial dysregulation and cell death in H9C2 rat cardiomyoblasts (H9C2-rCM) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Cardiomyocytes were exposed to acute or chronic treatment (5–60 min or 48 h) of vehicle control (0.0001 % Ultrapure Milli-Q water), hydrogen peroxide (100 μM) ± MitoQ (1 μM) or dTPP (1 μM) control. Hydrogen peroxide-induced overproduction of ROS, extracellular superoxide, mitochondrial ROS, mitochondrial hyperpolarisation and cell death were significantly blunted by MitoQ, but not dTPP, suggesting that the coenzyme Q₁₀ moiety of MitoQ is protective under these conditions. Interestingly, both MitoQ and dTPP exhibited a pro-mitochondrial fusion effect by preserving mitochondrial network and reducing mitochondrial fragmentation in oxidative stress conditions. Overall, our findings confirm the cytoprotective potential of MitoQ to limit oxidative stress-induced adverse mitochondrial remodelling and dysregulation that is clinically observed in cardiometabolic-induced cardiac dysfunction in the failing heart.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100469"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523310","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":"Semaphorin 3F is elevated in serum of heart failure patients and inhibits cardiac angiogenesis via the VEGF/Akt/eNOS pathway","authors":"Diana Petrova ,&nbsp;Miki Weberbauer ,&nbsp;Stephanie Reichert ,&nbsp;Stephanie Scheid ,&nbsp;Jennifer Esser ,&nbsp;Katrin Fink ,&nbsp;Daniel Duerschmied ,&nbsp;Martin Moser ,&nbsp;Thomas Helbing","doi":"10.1016/j.jmccpl.2025.100470","DOIUrl":"10.1016/j.jmccpl.2025.100470","url":null,"abstract":"<div><div>Left ventricular (LV) remodeling in heart failure (HF) is associated with vascular rarefaction and impaired angiogenesis. The inhibition of vascular endothelial growth factor (VEGF)-mediated angiogenesis is a key feature in the pathophysiology of HF. Semaphorin (Sema) 3F is a known inhibitor of VEGF signaling, but its role in HF remains to be elucidated.</div><div>Serum Sema3F levels were measured in HF patients (<em>n</em> = 70) by ELISA and were compared to those in patients with coronary artery disease (CAD, <em>n</em> = 26). Sema3F levels were significantly increased in HF patients. Sema3F RNA and protein expression were upregulated by hypoxia in cardiac endothelial cells (HCECs) as demonstrated by quantitative RT-PCR and Western blotting (WB). In Matrigel® sprouting assays, endothelial cell sprouting and branching were decreased in response to HF patient serum, suggesting that HF serum contains anti-angiogenic factors. Recombinant human Sema3F attenuated VEGF-mediated angiogenesis in Matrigel® sprouting, spheroid sprouting and aortic ring assays. Vice versa, siRNA-based Sema3F knockdown promoted angiogenesis. In zebrafish, morpholino-based Sema3F knockdown led to increased mortality and induced a vascular phenotype. Mechanistically, Sema3F inhibited VEGF-induced Akt and eNOS phosphorylation in endothelial cells, and Sema3F knockdown increased phosphorylation of Akt and eNOS.</div><div>Sema3F is elevated in serum of HF patients and has anti-angiogenic properties in cardiac angiogenesis through inhibition of the VEGF/Akt/eNOS pathway. Thus, targeting Sema3F could present a therapeutic approach to advanced HF in the future.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100470"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490446","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":"Combined genome and transcriptome analysis identifies molecular signatures of aortic disease in patients with Marfan syndrome","authors":"Katherine B. Stanley ,&nbsp;Alexa V. Mederos ,&nbsp;Ethan H. Barksdale ,&nbsp;Joel S. Corvera ,&nbsp;Joshua L. Davis ,&nbsp;Fang Fang ,&nbsp;Hongyu Gao ,&nbsp;Courtney E. Vujakovich ,&nbsp;Yunlong Liu ,&nbsp;Stephanie M. Ware ,&nbsp;Benjamin J. Landis","doi":"10.1016/j.jmccpl.2025.100467","DOIUrl":"10.1016/j.jmccpl.2025.100467","url":null,"abstract":"<div><h3>Introduction</h3><div>Transcriptional dysregulation in patients with Marfan syndrome (MFS) is complex and not well-defined. There are likely patient-specific and general mechanisms in the aortic pathology. In this study, we combine genome and transcriptome data from patients with MFS to determine the transcriptional impacts of disease-causing variants in <em>FBN1</em>.</div></div><div><h3>Methods</h3><div>Prospectively enrolled participants provided blood and aortic tissue samples. Smooth muscle cells (SMCs) were cultured directly from the proximal aortic tissues of MFS cases undergoing aortic root replacement and controls during heart transplant. Genome sequencing (GS) analysis was combined with mRNA-sequencing (mRNA-seq) and single-cell gene expression profiling of SMCs. Findings in SMC culture analysis were further investigated in primary frozen aortic tissues.</div></div><div><h3>Results</h3><div>Automatic annotation of single-cell expression profiles classified 99% of cultured cells as SMCs. All disease-causing <em>FBN1</em> variants were detected in both GS and SMC mRNA-seq reads. These included missense single nucleotide variants (SNVs), a whole-exon deletion, and a predicted stopgain SNV. Gene and allelic expression abnormalities in <em>FBN1</em> were identified. Broadly, genes that were dysregulated in MFS were enriched for glycerophospholipid metabolism, immune, potassium channel, and extracellular matrix processes. Single-cell clustering analysis identified subtypes of SMCs. Some genes were differentially expressed in MFS across multiple SMC subtypes (e.g. <em>TRPV2</em>), whereas others were significant within specific SMC states (e.g. <em>TGFB2</em> in SMCs expressing inflammatory markers).</div></div><div><h3>Conclusions</h3><div>mRNA-seq analysis of SMCs accurately identified <em>FBN1</em> variants. General and patient-specific effects on allelic and gene expression were identified. Metabolism of glycerophospholipids may be dysregulated in aortic SMCs in MFS. Identifying pathogenic features with transcriptome analysis may guide novel diagnostic and therapeutic strategies.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100467"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501321","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":"Bioinformatics tools for drug repurposing: a tutorial using heart failure as a case study","authors":"Ivo Fonseca ,&nbsp;Fábio Trindade ,&nbsp;Mário Santos ,&nbsp;Adelino Leite-Moreira ,&nbsp;Daniel Moreira-Gonçalves ,&nbsp;Rui Vitorino ,&nbsp;Rita Ferreira ,&nbsp;Rita Nogueira-Ferreira","doi":"10.1016/j.jmccpl.2025.100460","DOIUrl":"10.1016/j.jmccpl.2025.100460","url":null,"abstract":"<div><h3>Purpose</h3><div>Drug repurposing is a crucial strategy for researchers worldwide to accelerate drug development and mitigate associated risks and costs. Heart failure (HF) is a major global health problem with high prevalence and mortality rates. There are significant sex differences in HF, including in the risk factors and phenotype, which demand a sex-personalized drug treatment. A convenient approach in that direction is the reuse of drugs already approved for other conditions that are known to interact in sex-biased dysregulated pathways in HF. Numerous bioinformatics tools can help identify those candidates. This tutorial explores the utility of specific bioinformatics tools in identifying drugs to treat HF as a case study.</div></div><div><h3>Methods</h3><div>Herein, we explain how NeDRex helps identify genes associated with disease and drug repurposing and how functional enrichment analysis can be performed with ShinyGO. We also explain how to predict targets of small bioactive molecules with SwissTargetPrediction and how to retrieve known and predicted interactions between chemicals and proteins with STITCH.</div></div><div><h3>Results</h3><div>The tutorial demonstrates the use of these tools in searching for new HF treatments.</div></div><div><h3>Conclusion</h3><div>This tutorial is designed to ease entry into the utilization of the mentioned bioinformatics tools. This approach can also set a precedent for applying such tools to other diseases. The results presented in this tutorial are illustrative and do not constitute definitive evidence. They are intended for demonstration purposes only.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100460"},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322791","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}