Journal of molecular and cellular cardiology plus最新文献

{"title":"In-depth proteomic profiling identifies potentiation of the LPS response by 7-ketocholesterol","authors":"Iain R. Phair ,&nbsp;Magdalena Sovakova ,&nbsp;Noor Alqurashi ,&nbsp;Raid B. Nisr ,&nbsp;Alison D. McNeilly ,&nbsp;Douglas Lamont ,&nbsp;Graham Rena","doi":"10.1016/j.jmccpl.2025.100285","DOIUrl":"10.1016/j.jmccpl.2025.100285","url":null,"abstract":"<div><div>In patients with stable coronary artery disease, plasma levels of 7-ketocholesterol (7-KC), found at high levels in atherosclerotic lesions, predict risk of incident heart failure dose dependently, potentially contributing to disease aetiology. Previous studies demonstrated that 7-KC can elicit effects on macrophage function; however, effects of 7-KC on the macrophage proteome have not been studied systematically. Here we used quantitative mass spectrometry to establish the effect of 7-KC on the mouse macrophage proteome. 7-KC independently mediated dynamic changes, including on atherogenic/M1 markers, cholesterol metabolism, biosynthesis and transport, as well as nutrient transport more broadly. These changes were however insufficient alone to drive changes in cytokine and chemokine secretion. Rather, they prime the macrophage, potentiating LPS-stimulated TNF alpha secretion and key pro-inflammatory enzymes. Our results indicate that 7-KC has independent metabolic effects on the macrophage; however, effects on the immune system are primarily due to the changes in metabolism priming the response to an inflammatory stimulus. Earlier findings from CANTOS and the recent FDA approval of colchicine highlight that inflammation is a viable target for cardiovascular disease; however, it is currrently unclear which will be the best anti-inflammatory targets to pursue in the future. In this context, our findings suggest that drugs targeting atherogenic markers induced by 7-KC might be well tolerated, as they will not necessarily be expected to be immunosuppressive.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100285"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164833","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":"Circulating levels of miR-20b-5p are associated with survival in cardiogenic shock","authors":"Tuomas Mäntylä ,&nbsp;Chunguang Wang ,&nbsp;Mikko Hänninen ,&nbsp;Katariina Immonen ,&nbsp;Toni Jäntti ,&nbsp;Johan Lassus ,&nbsp;Ilkka Tikkanen ,&nbsp;Kari Pulkki ,&nbsp;Yvan Devaux ,&nbsp;Veli-Pekka Harjola ,&nbsp;Päivi Lakkisto ,&nbsp;CardShock Study Investigators","doi":"10.1016/j.jmccpl.2025.100284","DOIUrl":"10.1016/j.jmccpl.2025.100284","url":null,"abstract":"<div><div>Cardiogenic shock (CS) is a medical emergency with high in-hospital mortality. New biomarkers are needed to identify patients at a greater risk of adverse outcomes. This study aimed to investigate the prognostic potential of microRNAs (miRNAs) in assessment of the outcome of cardiogenic shock.</div><div>Circulating miRNA levels were measured by quantitative PCR in plasma samples collected at baseline from 165 patients of the multicenter, prospective, observational CardShock study and compared between in-hospital and 90-day survivors and non-survivors. Of the 10 studied miRNAs, median levels of miR-20b-5p at baseline were significantly higher in in-hospital and 90-day survivors compared to non-survivors [median 0.014 arbitrary units (AU) (interquartile range (IQR) 0.003–0.024) <em>vs.</em> 0.008 AU (IQR 0.001–0.015), <em>p</em> = 0.013] and [0.015 AU (IQR 0.003–0.025) <em>vs.</em> 0.010 AU (IQR 0.001–0.015), <em>p</em> = 0.012], respectively. In Cox regression analysis, miR-20b-5p levels in the highest quartile were significantly associated with 90-day survival (adjusted hazard ratio 2.47 (95 % confidence interval 1.16–5.28), <em>p</em> = 0.019) when adjusted for CardShock Risk Score variables (age, confusion at presentation, previous myocardial infarction or coronary artery bypass grafting, acute coronary syndrome (ACS) etiology, left ventricular ejection fraction, lactate, and estimated glomerular filtration rate). A similar association of highest quartile miR-20b-5p levels with 90-day survival was also confirmed in ACS patient subcohort (79 % of CS patients).</div><div>The results of this study indicate that circulating levels of miR-20b-5p at baseline could help in assessing in-hospital and 90-day survival in CS patients.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100284"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164832","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":"Deep plasma and tissue proteome profiling of knockout mice reveals pathways associated with Svep1 deficiency","authors":"Colleen B. Maxwell ,&nbsp;Nikita Bhakta ,&nbsp;Matthew J. Denniff ,&nbsp;Jatinderpal K. Sandhu ,&nbsp;Thorsten Kessler ,&nbsp;Leong L. Ng ,&nbsp;Donald J.L. Jones ,&nbsp;Tom R. Webb ,&nbsp;Gavin E. Morris","doi":"10.1016/j.jmccpl.2025.100283","DOIUrl":"10.1016/j.jmccpl.2025.100283","url":null,"abstract":"<div><div>Despite strong causal associations with cardiovascular and metabolic disorders including coronary artery disease, hypertension, and type 2 diabetes, as well as a range of other diseases, the exact function of the protein SVEP1 remains largely unknown. Animal models have been employed to investigate how SVEP1 contributes to disease, with a focus on murine models exploring its role in development, cardiometabolic disease and platelet biology. In this study, we aimed to comprehensively phenotype the proteome of <em>Svep1</em>^+/− mice compared to wild-type (WT) littermates using liquid chromatography-tandem mass spectrometry (LC-MS/MS) bottom-up proteomics in plasma, heart, aorta, lung, and kidney to identify dysregulated pathways and biological functions associated with <em>Svep1</em> deficiency. Our findings reveal that <em>Svep1</em> deficiency leads to significant proteomic alterations across the mouse, with the highest number of dysregulated proteins observed in plasma and kidney. Key dysregulated proteins in plasma include upregulation of ADGRV1, CDH1, and MYH6, and downregulation of MTIF2 and AKAP13 which, alongside other proteins dysregulated across tissues, indicate disruption in cell adhesion, extracellular matrix organisation, platelet degranulation, and Rho GTPase pathways. Novel findings include significant enrichment of complement cascades in plasma, suggesting dysregulation of innate immune responses and hemostasis due to <em>Svep1</em> deficiency. Pathways related to chylomicron assembly and lipid metabolism were also enriched. Additionally, we developed a high-throughput quantitative targeted LC-MS/MS assay to measure endogenous levels of murine SVEP1. SVEP1 was detectable in lung homogenate and showed a significant reduction in SVEP1 levels in <em>Svep1</em>^+/− <em>vs.</em> WT, but was not identified in plasma, heart, aorta, or kidney, likely due to expression levels below the assay's detection limit. Overall, this deep phenotyping study provides insight into the systemic impact of <em>Svep1</em> deficiency.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100283"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082602","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":"Integrated transcriptomic and regulatory RNA profiling reflects complex pathophysiology and uncovers a conserved gene signature in end stage heart failure","authors":"Amit Anand ,&nbsp;Julius Punnen ,&nbsp;U.M. Nagamalesh ,&nbsp;Sabariya Selvam ,&nbsp;Madhusudhan Bysani ,&nbsp;Ramya Venkatesh ,&nbsp;Kriti Nawin ,&nbsp;Shilpa Garg ,&nbsp;Bagirath Raghuraman ,&nbsp;Varun Shetty ,&nbsp;Senthil Kumaran ,&nbsp;Manoj Dokania ,&nbsp;Pradeep Narayan ,&nbsp;Ankita Udwadia ,&nbsp;Kushan Gunawardhana ,&nbsp;David Gordon ,&nbsp;Manjunath Ramarao ,&nbsp;Lei Zhao ,&nbsp;Jyoti Gulia","doi":"10.1016/j.jmccpl.2025.100282","DOIUrl":"10.1016/j.jmccpl.2025.100282","url":null,"abstract":"<div><h3>Background</h3><div>Heart failure (HF) is a complex syndrome. Despite availability of multiple treatment options, the mortality remains high and the quality of life poor. Better understanding of the underlying pathophysiological processes can lead to development of novel therapies. Multiple comparative transcriptomics studies, which revealed gene level changes in the key pathophysiological pathways in failing hearts, point towards heterogeneity from interplay of disease stage, etiologies and ethnicity. Transcriptomic characterization of HF in patients from different ethnicities can potentially help in understanding the heterogeneity imparted by various factors and the core elements in heart failure.</div></div><div><h3>Methods &amp; results</h3><div>An integrated analysis of bulk transcriptome and microRNA sequencing from the cardiac tissues of 30 South Asian (SA) patients having HF with reduced ejection fraction (HFrEF) and 19 control subjects was conducted. Plasma miRNAs from a subset of HFrEF and control patients were also sequenced to understand their biomarker potential. The altered transcriptome from the myocardium of SA HFrEF patients reflected cardiac muscle contraction, cellular energetics, altered immune signaling and extracellular matrix remodelling as predominant pathophysiological mechanisms. The SA HFrEF patients also showed dysregulation of multiple microRNAs in cardiac tissue like miR-216, miR-217, miR-184 and miR-9983. Many of these miRNAs, such as miR184 and few others, showed altered levels in both the plasma and cardiac tissue of HFrEF patients suggesting their biomarker potential. The diversity in the HFrEF transcriptomes from published studies led us to examine the core HF genes in our cohort. A gene signature generated using machine learning (ML) from the top dysregulated genes in SA HFrEF cohort stratified HF from controls in other cohorts. The sensitivity of the HF gene signature was further improved when union of two cohorts was used as a training set. Our ML analyses developed a core HF gene signature consisting of 21 genes that can stratify HF patients from controls with 98 % sensitivity in all the tested cohorts.</div></div><div><h3>Conclusions</h3><div>This study reveals molecular changes underlying the pathophysiology as reflected by coding and regulatory non-coding components of transcriptome from South Asian patients and uncovers a conserved gene signature for HF.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100282"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164831","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":"Rostafuroxin, the inhibitor of endogenous ouabain, ameliorates chronic undernutrition-induced hypertension, stroke volume, cardiac output, left-ventricular fibrosis and alterations in Na+-transporting ATPases in rats","authors":"Amaury Pereira-Acácio ,&nbsp;João P.M. Veloso-Santos ,&nbsp;Camile O. Silva-Rodrigues ,&nbsp;Debora Mello ,&nbsp;Danilo S. Alves-Bezerra ,&nbsp;Glória Costa-Sarmento ,&nbsp;Humberto Muzi-Filho ,&nbsp;Carlla A. Araújo-Silva ,&nbsp;Jarlene A. Lopes ,&nbsp;Christina M. Takiya ,&nbsp;Sergian V. Cardozo ,&nbsp;Adalberto Vieyra","doi":"10.1016/j.jmccpl.2024.100281","DOIUrl":"10.1016/j.jmccpl.2024.100281","url":null,"abstract":"<div><div>Our aim has been to investigate the effect of Rostafuroxin, an inhibitor of endogenous cardiotonic steroids (EO/CTS), on cardiac structure and function and cardiac Na⁺ transport in undernourished hypertensive Wistar rats, and to determine whether chronic undernutrition is a modifiable risk factor for cardiovascular-kidney-metabolic (CKM) syndrome. Echocardiographic studies evaluated stroke volume cardiac output, ejection fraction, mitral valve early diastolic blood flow/late diastolic blood flow (E/A) ratio, and right renal resistive index. The cardiomyocyte area and collagen infiltration of cardiac tissue were investigated, as also the activities of the cardiac ouabain-sensitive (Na⁺+K⁺)ATPase ((Na⁺+K⁺)ATPase Sens) and ouabain-resistant Na⁺-ATPase (Na⁺-ATPase Res). Undernourished hypertensive rats presented tachycardia, reduced stroke volume, decreased cardiac output, preserved fractional shortening and ejection fraction, unmodified mitral valve E/A ratio, and increased right renal resistive index. Cardiomyocyte size decreased and intense collagen infiltration had occurred. The (Na⁺+K⁺)ATPase Sens activity decreased, whereas that of Na⁺-ATPase Res increased. Rostafuroxin selectively modified some of these echocardiographic and molecular parameters: it increased stroke volume and cardiac output and prevented histopathological alterations. The drug decreased and increased the activities of (Na⁺+K⁺)ATPase Sens and Na⁺-ATPase Res, respectively, in normonourished rats, and the opposite trend was found in the undernourished group. It is concluded that chronic undernutrition in rats can provoke structural, functional, histological, and molecular cardiovascular alterations that, with the simultaneous changes in renal parameters described in this and in previous studies, configure an undescribed type of CKM syndrome. The data also demonstrate that the blockade of EO/CTS ameliorates stroke volume and cardiac output, thus preventing or delaying the worsening of the syndrome.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100281"},"PeriodicalIF":0.0,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164834","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":"Association of LEF1-AS1 with cardiovascular and neurological complications of COVID-19","authors":"Mélanie Vausort ,&nbsp;Andrew I. Lumley ,&nbsp;Hassina Boubakeur ,&nbsp;Lu Zhang ,&nbsp;Feng Q. Hefeng ,&nbsp;Markus Ollert ,&nbsp;Paul Wilmes ,&nbsp;Guy Fagherazzi ,&nbsp;Yvan Devaux","doi":"10.1016/j.jmccpl.2024.100280","DOIUrl":"10.1016/j.jmccpl.2024.100280","url":null,"abstract":"<div><div>A significant proportion of COVID-19 patients develop long-term complications, particularly cardiovascular and neurological issues. Even though risk factors for developing complications after COVID-19 have been identified, a biomarker to predict these complications could enable personalized healthcare and potentially reduce the disease burden. Easily measurable in the blood, the long noncoding RNA LEF1-AS1 has recently been associated with in-hospital mortality following SARS-CoV − 2 infection and holds potential as a biomarker for disease severity in COVID-19 patients. Consequently, we examined LEF1-AS1's ability to predict cardiovascular and neurological complications after COVID-19. LEF1-AS1 has been measured in the blood by quantitative PCR in 104 primo-infected participants from the Predi-COVID cohort within 3 days post clinical PCR-confirmed COVID-19 diagnosis. Among them, 35 participants (34 %) reported at least one persistent cardiovascular symptom and at least one persistent neurological or ocular symptom in a self-administered questionnaire 12 months after COVID-19 diagnosis. Blood levels of LEF1-AS1 at baseline in these patients were lower (<em>p</em> = 0.019) compared to those who did not report symptoms. Lower LEF1-AS1 levels were associated with symptoms with an odds ratio of 0.48 (95 % confidence interval 0.28–0.83) in a logistic regression model adjusted for age, sex, comorbidity, and moderate disease severity at baseline. LEF1-AS1 expression was positively correlated with the frequency of naïve T cells and negatively correlated with the frequency of effector memory T cells among total CD8+ T cells, revealing a potential association between LEF1-AS1 and CD8+ T-cell differentiation following SARS-CoV-2 infection. In conclusion, blood levels of LEF1-AS1 can potentially help in predicting 12-month cardiovascular and neurological complications in COVID-19 patients, though this finding requires validation in larger cohorts.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164182","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":"Circulating autophagy regulator Rubicon is linked to increased myocardial infarction risk","authors":"Marie-Hélène Grazide ,&nbsp;Jean-Bernard Ruidavets ,&nbsp;Wim Martinet ,&nbsp;Meyer Elbaz ,&nbsp;Cécile Vindis","doi":"10.1016/j.jmccpl.2024.100279","DOIUrl":"10.1016/j.jmccpl.2024.100279","url":null,"abstract":"<div><h3>Background</h3><div>The identification of new biomarkers that improve existing cardiovascular risk prediction models for acute coronary syndrome is essential for accurately identifying high-risk patients and refining treatment strategies. Autophagy, a vital cellular degradation mechanism, is important for maintaining cardiac health. Dysregulation of autophagy has been described in cardiovascular conditions such as myocardial ischemia-reperfusion injury, a key factor in myocardial infarction (MI). Recently, Rubicon (Run domain Beclin-1-interacting and cysteine-rich domain-containing protein), a key negative regulator of autophagy, has been identified in the modulation of cardiac stress response.</div></div><div><h3>Objectives</h3><div>This study aimed to explore the relationship between circulating Rubicon levels and MI, and to evaluate the incremental predictive value of Rubicon when integrated into a clinical risk prediction model for MI.</div></div><div><h3>Results</h3><div>We analyzed plasma Rubicon concentrations in 177 participants, comprising type I MI patients and high-risk control subjects. Our results revealed significantly elevated plasma Rubicon levels in MI patients compared to the control group (126.5 pg/mL vs. 53 pg/mL, <em>p</em> &lt; 0.001). Furthermore, Rubicon levels showed a positive correlation with cardiovascular risk factors such as total cholesterol and LDL cholesterol. Multivariate analysis confirmed that Rubicon levels were independently associated with an increased risk of MI. The inclusion of Rubicon in traditional cardiovascular risk models notably enhanced predictive accuracy for MI, with the area under the curve (AUC) rising from 0.868 to 0.905 (<em>p</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>These findings suggest that Rubicon is a valuable biomarker associated with MI risk, providing additional predictive value beyond standard cardiovascular risk factors. This highlights the importance of Rubicon's critical role in the pathophysiology of CVD.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100279"},"PeriodicalIF":0.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973847","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":"Cardioprotective strategies in myocardial ischemia-reperfusion injury: Implications for improving clinical translation","authors":"Chao Tong ,&nbsp;Bingying Zhou","doi":"10.1016/j.jmccpl.2024.100278","DOIUrl":"10.1016/j.jmccpl.2024.100278","url":null,"abstract":"<div><div>Ischemic heart disease is the most common cause of death and disability globally which is caused by reduced or complete cessation of blood flow to a portion of the myocardium. One of its clinical manifestations is myocardial infarction, which is commonly treated by restoring of blood flow through reperfusion therapies. However, serious ischemia-reperfusion injury (IRI) can occur, significantly undermining clinical outcomes, for which there is currently no effective therapy. This review revisits several potential pharmacological IRI intervention strategies that have entered preclinical or clinical research phases. Here, we discuss what we have learned through translational failures over the years, and propose possible ways to enhance translation efficiency.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100278"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164063","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":"An optimized plasmalogen modulating dietary supplement provides greater protection in a male than female mouse model of dilated cardiomyopathy","authors":"Teleah G. Belkin ,&nbsp;Emma I. Masterman ,&nbsp;Gunes S. Yildiz ,&nbsp;Helen Kiriazis ,&nbsp;Natalie A. Mellett ,&nbsp;Jonathon Cross ,&nbsp;Kyah Grigolon ,&nbsp;Akshima Dogra ,&nbsp;Daniel Donner ,&nbsp;Roger Chooi ,&nbsp;Amy Liang ,&nbsp;Andrew R. Kompa ,&nbsp;Junichi Sadoshima ,&nbsp;Amanda J. Edgley ,&nbsp;David W. Greening ,&nbsp;Peter J. Meikle ,&nbsp;Yow Keat Tham ,&nbsp;Julie R. McMullen","doi":"10.1016/j.jmccpl.2024.100273","DOIUrl":"10.1016/j.jmccpl.2024.100273","url":null,"abstract":"<div><div>We previously reported that plasmalogens, a class of phospholipids, were decreased in a setting of dilated cardiomyopathy (DCM). Plasmalogen levels can be modulated via a dietary supplement called alkylglycerols (AG) which has demonstrated benefits in some disease settings. However, its therapeutic potential in DCM remained unknown. To determine whether an optimized AG supplement could restore plasmalogen levels and attenuate cardiac dysfunction/pathology, we placed a cardiac-specific transgenic DCM mouse model of both sexes on chow +/−1.5 % AG supplementation at ∼10 weeks of age for 16 weeks. Cardiac function was assessed by echocardiography, tissues were collected for histological and molecular analyses including lipidomics and proteomics via liquid chromatography-mass spectrometry. AG supplementation increased total plasmalogens in DCM hearts and attenuated lung congestion of both sexes, but only prevented cardiac dysfunction in males. This was associated with attenuated cardiac and renal enlargement, a more favorable pro-cardiac gene expression profile, and a trend for lower cardiac fibrosis. By lipidomics, specific d18:1 ceramide species associated with cardiac pathology were lower in the DCM hearts from mice on the AG diet, and tetralinoleoyl cardiolipins, a lipid crucial for mitochondrial function was restored with AG supplementation. Proteomic analysis of hearts from male DCM mice receiving AG supplementation revealed enrichment in mitochondrial protein network, as well as upregulation of extracellular matrix binding proteins including agrin, a protein associated with cardiac regeneration. In summary, AG supplementation restored plasmalogens in DCM hearts but showed greater therapeutic potential in males than females.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"11 ","pages":"Article 100273"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973846","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":"10038: Myosin Inhibition using mavacamten facilitates relaxation and improves compliance of the myofibrils from the HFpEF heart","authors":"YH Lin,&nbsp;EP Yap,&nbsp;S Cong,&nbsp;G Sivakumar,&nbsp;NGZ Tee,&nbsp;CJA Ramachandra,&nbsp;DJ Hausenloy","doi":"10.1016/j.jmccpl.2024.100160","DOIUrl":"10.1016/j.jmccpl.2024.100160","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"10 ","pages":"Article 100160"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143175540","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}