Journal of molecular and cellular cardiology plus最新文献

{"title":"Wnt/β-catenin signaling regulates cardiac Cx43 in a metabolic substrate-dependent manner","authors":"Omar Kayyem ,&nbsp;Ruonan Gu ,&nbsp;Ying Xia ,&nbsp;Jerry Wang ,&nbsp;Aizhu Lu ,&nbsp;Hongwei Wang ,&nbsp;Darryl R. Davis ,&nbsp;Peter Liu ,&nbsp;Wenbin Liang","doi":"10.1016/j.jmccpl.2025.100488","DOIUrl":"10.1016/j.jmccpl.2025.100488","url":null,"abstract":"<div><h3>Background</h3><div>Both Na_v1.5 and Cx43 are critical for the fast electrical impulse conduction in the myocardium and their reductions create the arrhythmogenic substrate. Wnt/β-catenin signaling is activated in arrhythmogenic myocardium, and although this signaling is known to downregulate cardiac Na_v1.5, its regulation of Cx43 is unclear as conflicting results have been reported. The present study investigated how Wnt/β-catenin signaling regulates Cx43 in rat and human cardiomyocytes and if it is dependent on the sex of the cells or the metabolic substrates.</div></div><div><h3>Methods</h3><div>Male and female neonatal rat ventricular myocytes (NRVMs) were treated with CHIR-99021 (CHIR) or Wnt3a protein, two different activators of the Wnt/β-catenin signaling, either in a medium rich in glucose (a preferred metabolic substrate in heart failure) or in a medium rich in lipid (∼150 μM fatty acid, a preferred substrate in healthy hearts). Both healthy and Brugada Syndrome human iPSC-derived cardiomyocytes (iPSC-CMs) were used to confirm observations in NRVMs.</div></div><div><h3>Results</h3><div>When maintained in a glucose-rich medium, <em>Gja1</em> mRNA (encoding Cx43) was reduced by a low concentration of CHIR (1 μM) in female NRVMs but only at a high concentration of CHIR (10 μM) in male NRVMs. However, reductions in Cx43 protein were observed at 1 μM CHIR in both male and female NRVMs, suggesting the involvement of both transcriptional and post-transcriptional mechanisms. When maintained in a lipid-rich medium, neither <em>Gja1</em> mRNA nor Cx43 protein was altered by CHIR at 1 or 3 μM. In contrast, CHIR-induced reductions in <em>Scn5a</em> mRNA and Na_v1.5 protein were observed in both glucose-rich and lipid-rich media, with no significant sex-specific differences detected. Consistent with studies using CHIR, which is a Wnt receptor-independent activator, Wnt3a protein also reduced both <em>Gja1</em> mRNA and Cx43 protein in NRVMs in the glucose-rich medium but not in the lipid-rich medium. In human iPSC-CMs from two healthy volunteers and one Brugada Syndrome patient, Wnt/β-catenin signaling activation reduced <em>GJA1</em> mRNA and Cx43 protein in a standard, glucose-containing medium.</div></div><div><h3>Conclusions</h3><div>These data demonstrate that metabolic substrates regulate the effects of Wnt/β-catenin signaling in cardiomyocytes, with reductions in Cx43 mRNA and protein only observed when glucose is the primary metabolic substrate, which occurs in arrhythmogenic conditions such as cardiac hypertrophy and heart failure.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"14 ","pages":"Article 100488"},"PeriodicalIF":2.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269404","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":"Ac-SDKP and eplerenone confer additive cardioprotection against angiotensin II-induced cardiac injury in C57BL/6J mice","authors":"Suhail Hamid ,&nbsp;Sarah Sarkar ,&nbsp;Hongmei Peng ,&nbsp;Matrougui Khalid ,&nbsp;Pablo A. Ortiz ,&nbsp;Jiang Xu ,&nbsp;Tang-Dong Liao ,&nbsp;Robert A. Knight ,&nbsp;Nour-Eddine Rhaleb","doi":"10.1016/j.jmccpl.2025.100485","DOIUrl":"10.1016/j.jmccpl.2025.100485","url":null,"abstract":"<div><div>Eplerenone, a mineralocorticoid receptor antagonist, is an anti-hypertensive and cardioprotective drug. We showed that N-Acetyl-Seryl-Aspartyl-Proline (Ac-SDKP) exerts beneficial effects on the heart. Whether Ac-SDKP provides additional cardioprotective effects if combined with eplerenone in angiotensin II (Ang II)-induced hypertension remains unknown. Male C57BL/6J mice were treated with either sham, Ang II (2.9 mg/kg/day, s.c.), Ang II + Ac-SDKP (1.6 mg/kg/day, s.c.), Ang II + Eplerenone (150 mg/kg/day in mouse chow), or Ang II + Ac-SDKP + Eplerenone. Treatment lasted for eight weeks. Systolic blood pressure (SBP) measurements were taken weekly. Echocardiography (Echo) and magnetic resonance imaging (MRI) were performed at the end of the experiment. SBP was increased in all mice with Ang II and was not affected by any treatment. Posterior wall thickness (PWT) and left ventricular (LV) mass were increased in Ang II–treated groups. LV mass was not significantly affected by treatment, but PWT was reduced by both monotherapies and showed the greatest reduction with combined Ac-SDKP and eplerenone. Ejection fraction (EF) decreased in the Ang II group compared to the sham group. EF increased with all treatments (MRI), and there was a further significant increase in EF for mice treated with Ac-SDKP + Eplerenone compared to those receiving a single treatment (Echo). Our data indicate that treatment with Ac-SDKP or Eplerenone improves cardiac function in Ang II-induced hypertension, and supplying Ac-SDKP to Eplerenone provides additive, not synergistic, cardioprotective effects. These beneficial effects were associated with decreased myocardial collagen accumulation, CD68-positive macrophage infiltration, and the expression of CHOP, an endoplasmic reticulum stress mediator. Ac-SDKP could be an effective supplementary treatment alongside Eplerenone for managing hypertension-associated cardiac damage and dysfunction.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"14 ","pages":"Article 100485"},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121059","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":"Single-cell dynamics reveal a stress-induced decision between hypertrophy and apoptosis in neonatal rat cardiomyocytes","authors":"Bryan Chun ,&nbsp;Lavie Ngo ,&nbsp;Jeffrey J. Saucerman","doi":"10.1016/j.jmccpl.2025.100484","DOIUrl":"10.1016/j.jmccpl.2025.100484","url":null,"abstract":"<div><div>Cardiomyocyte hypertrophy and apoptosis underlie cardiomyopathies and heart failure. While previous studies have reported both hypertrophy and apoptosis at the population level, how individual cells commit to these distinct analog and digital fates is unclear. To elucidate how individual cells decide to grow and/or die, we developed a high-content microscopy approach to track single-cell dynamics of neonatal rat cardiomyocytes. Even untreated cells exhibited substantial single-cell variability in growth and death. Uniform treatments of staurosporine or phenylephrine induced distinctive morphological programs resulting in apoptosis and hypertrophy, respectively, but only in cell subpopulations. Increasing concentrations of the β-adrenergic receptor agonist isoproterenol caused a population-level biphasic induction of hypertrophy and then apoptosis, consistent with either apoptosis in the most hypertrophic cells (a grow-and-die model) or an early decision between hypertrophy and delayed apoptosis (a grow-or-die model). By tracking single-cell fates, we found that when stressed with either isoproterenol or phenylephrine, individual cells that hypertrophy are protected from later apoptosis. Further, caspase 3 inhibition shifted the single-cell probability from apoptosis to hypertrophy fates. Machine learning models found that a cell's initial size and DNA content or condensation could predict a cell's bias for hypertrophy or apoptosis. Together, these data support a grow-or-die conceptual model for cardiomyocyte decisions. This single-cell profiling method for tracking joint analog-digital cell decisions reveals that despite hypertrophy and apoptosis co-occurring at the population level, individual cardiomyocytes decide early whether to grow or die.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"14 ","pages":"Article 100484"},"PeriodicalIF":2.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145098883","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":"Systemic administration of analgesic buprenorphine, but not carprofen, affects cardiomyocyte contractility in rodents","authors":"Inez Duursma ,&nbsp;Valentijn Jansen ,&nbsp;Nicole Zaat ,&nbsp;Tyler J. Kirby ,&nbsp;Jolanda van der Velden ,&nbsp;Diederik W.D. Kuster","doi":"10.1016/j.jmccpl.2025.100482","DOIUrl":"10.1016/j.jmccpl.2025.100482","url":null,"abstract":"<div><div>Rodents are often used in cardiac research, where they undergo a wide variety of procedures. To ensure animal welfare, the rodents are often analgesized before, during and/or after a procedure. Contractility measurements in isolated murine cardiomyocytes are an often used method to assess function; however, little is known about the effects of analgesia on this. Therefore, we investigated the effect of systemic injection of a non-steroidal anti-inflammatory drug, carprofen (<em>N</em> = 3 mice, <em>n</em> = 273 CMs; N = 3 rats, <em>n</em> = 241 CMs) and an opioid, buprenorphine (<em>N</em> = 4 mice, <em>n</em> = 326 CMs; N = 4 rats, <em>n</em> = 308 CMs) on isolated cardiomyocytes using unloaded contractility measurements. We found that buprenorphine prolongs the relaxation of cardiomyocytes, an effect confound to the first 3 h post-isolation, whereas carprofen does not affect contractility. As analgesia might influence the stress response, we assessed the influence of carprofen and buprenorphine on the β-adrenergic receptor (AR) response. The response of cardiomyocytes to both a β-AR agonist and antagonist was not affected by carprofen or buprenorphine. <em>In vitro</em> addition of the analgesics to rat cardiomyocytes (<em>N</em> = 3 rats, <em>n</em> = 197 CMs saline, <em>n</em> = 214 CMs carprofen, <em>n</em> = 211 CMs buprenorphine) revealed that the effect of buprenorphine on contractility is caused by a systemic response rather than a direct response of cardiomyocytes specifically. Collectively, our results suggest that carprofen and buprenorphine do not affect isolated cardiomyocyte contractility if measurements are performed at least 4 h post-isolation.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"14 ","pages":"Article 100482"},"PeriodicalIF":2.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160042","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":"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":"JMCC plus receives first impact factor","authors":"Davor Pavlovic ,&nbsp;Rebekah Gundry","doi":"10.1016/j.jmccpl.2025.100480","DOIUrl":"10.1016/j.jmccpl.2025.100480","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100480"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095286","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":"Cocaine and the heart – bad news for risk/reward","authors":"Jules C. Hancox,&nbsp;Andrew F. James","doi":"10.1016/j.jmccpl.2025.100477","DOIUrl":"10.1016/j.jmccpl.2025.100477","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"13 ","pages":"Article 100477"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095287","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}