Journal of molecular and cellular cardiology plus最新文献

{"title":"Unveiling the neural remodelling landscape in failure heart: A new frontier in cardiac arrhythmogenesis research","authors":"A. Grassam-Rowe, M. 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":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44651730","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":"Metformin preconditioning protects against myocardial stunning and preserves protein translation in a mouse model of cardiac arrest","authors":"Cody A. Rutledge ,&nbsp;Claudia Lagranha ,&nbsp;Takuto Chiba ,&nbsp;Kevin Redding ,&nbsp;Donna B. Stolz ,&nbsp;Eric Goetzman ,&nbsp;Sunder Sims-Lucas ,&nbsp;Brett A. Kaufman","doi":"10.1016/j.jmccpl.2023.100034","DOIUrl":"10.1016/j.jmccpl.2023.100034","url":null,"abstract":"<div><p>Cardiac arrest (CA) causes high mortality due to multi-system organ damage attributable to ischemia-reperfusion injury. Recent work in our group found that among diabetic patients who experienced cardiac arrest, those taking metformin had less evidence of cardiac and renal damage after cardiac arrest when compared to those not taking metformin. Based on these observations, we hypothesized that metformin's protective effects in the heart were mediated by AMPK signaling, and that AMPK signaling could be targeted as a therapeutic strategy following resuscitation from CA. The current study investigates metformin interventions on cardiac and renal outcomes in a non-diabetic CA mouse model. We found that two weeks of metformin pretreatment protects against reduced ejection fraction and reduces kidney ischemia-reperfusion injury at 24 h post-arrest. This cardiac and renal protection depends on AMPK signaling, as demonstrated by outcomes in mice pretreated with the AMPK activator AICAR or metformin plus the AMPK inhibitor compound C.</p><p>At this 24-h time point, heart gene expression analysis showed that metformin pretreatment caused changes supporting autophagy, antioxidant response, and protein translation. Further investigation found associated improvements in mitochondrial structure and markers of autophagy. Notably, Western analysis indicated that protein synthesis was preserved in arrest hearts of animals pretreated with metformin. The AMPK activation-mediated preservation of protein synthesis was also observed in a hypoxia/reoxygenation cell culture model. Despite the positive impacts of pretreatment in vivo and in vitro, metformin did not preserve ejection fraction when deployed at resuscitation. Taken together, we propose that metformin's in vivo cardiac preservation occurs through AMPK activation, requires adaptation before arrest, and is associated with preserved protein translation.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"4 ","pages":"Article 100034"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b5/92/nihms-1911045.PMC10327679.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9865211","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":"90-day mortality risk related to postoperative potassium levels in patients undergoing coronary bypass surgery","authors":"Mikkel Kjeldgaard ,&nbsp;Mads Odgaard Mæng ,&nbsp;Christian Torp-Pedersen ,&nbsp;Peter Søgaard ,&nbsp;Kristian Hay Kragholm ,&nbsp;Jan Jesper Andreasen ,&nbsp;Maria Lukács Krogager","doi":"10.1016/j.jmccpl.2023.100035","DOIUrl":"10.1016/j.jmccpl.2023.100035","url":null,"abstract":"<div><h3>Aims</h3><p>While electrolyte depletion is known to occur during coronary artery bypass grafting (CABG) with extracorporeal circulation, little is known about the frequency of potassium disturbances following either on- or off-pump CABG and its association with mortality. We examined the frequency of potassium disturbances and the association of plasma potassium with mortality risk in patients following CABG.</p></div><div><h3>Methods and results</h3><p>From Danish National Registries, we identified 6123 adult patients (≥18 years old) undergoing first-time CABG, and who had a registered potassium measurement within 14 days before and 7 days after their surgery between 1995 and 2018. Using 4.0–4.6 mmol/L as reference, potassium was stratified into five predefined intervals: &lt;3.5, 3.5–3.9, 4.0–4.6, 4.7–5.0, and ≥5.1 mmol/L. We examined the absolute mortality risk and assessed the Cox proportional hazard model to analyze the 90-day all-cause mortality risk in relation to the first available post-operative potassium sample. Pre- and postoperative potassium disturbances were rare, while more common in patients with chronic kidney disease. The adjusted cox regression presented a trend of increased mortality only in hyperkalemia. The absolute mortality risk increased in hyperkalemia, hypokalemia and low-normokalemia, while high normokalemia presented a lesser relative risk of mortality, compared to the reference of 4.0–4.6 mmol/L.</p></div><div><h3>Conclusion</h3><p>Although the cox regression presented a trend of increased mortality only in hyperkalemia, the absolute mortality risk supported a strategy of careful monitoring and evaluation of any potassium disturbance, including in the lower normokalemia interval.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"4 ","pages":"Article 100035"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45761832","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":"RNAseq profiling of blood from patients with coronary artery disease: Signature of a T cell imbalance","authors":"Timothy A. McCaffrey ,&nbsp;Ian Toma ,&nbsp;Zhaoqing Yang ,&nbsp;Richard Katz ,&nbsp;Jonathan Reiner ,&nbsp;Ramesh Mazhari ,&nbsp;Palak Shah ,&nbsp;Zachary Falk ,&nbsp;Richard Wargowsky ,&nbsp;Jennifer Goldman ,&nbsp;Dan Jones ,&nbsp;Dmitry Shtokalo ,&nbsp;Denis Antonets ,&nbsp;Tisha Jepson ,&nbsp;Anastasia Fetisova ,&nbsp;Kevin Jaatinen ,&nbsp;Natalia Ree ,&nbsp;Maxim Ri","doi":"10.1016/j.jmccpl.2023.100033","DOIUrl":"10.1016/j.jmccpl.2023.100033","url":null,"abstract":"<div><h3>Background</h3><p>Cardiovascular disease had a global prevalence of 523 million cases and 18.6 million deaths in 2019. The current standard for diagnosing coronary artery disease (CAD) is coronary angiography either by invasive catheterization (ICA) or computed tomography (CTA). Prior studies employed single-molecule, amplification-independent RNA sequencing of whole blood to identify an RNA signature in patients with angiographically confirmed CAD. The present studies employed Illumina RNAseq and network co-expression analysis to identify systematic changes underlying CAD.</p></div><div><h3>Methods</h3><p>Whole blood RNA was depleted of ribosomal RNA (rRNA) and analyzed by Illumina total RNA sequencing (RNAseq) to identify transcripts associated with CAD in 177 patients presenting for elective invasive coronary catheterization. The resulting transcript counts were compared between groups to identify differentially expressed genes (DEGs) and to identify patterns of changes through whole genome co-expression network analysis (WGCNA).</p></div><div><h3>Results</h3><p>The correlation between Illumina amplified RNAseq and the prior SeqLL unamplified RNAseq was quite strong (r = 0.87), but there was only 9 % overlap in the DEGs identified. Consistent with the prior RNAseq, the majority (93 %) of DEGs were down-regulated ∼1.7-fold in patients with moderate to severe CAD (&gt;20 % stenosis). DEGs were predominantly related to T cells, consistent with known reductions in Tregs in CAD. Network analysis did not identify pre-existing modules with a strong association with CAD, but patterns of T cell dysregulation were evident. DEGs were enriched for transcripts associated with ciliary and synaptic transcripts, consistent with changes in the immune synapse of developing T cells.</p></div><div><h3>Conclusions</h3><p>These studies confirm and extend a novel mRNA signature of a Treg-like defect in CAD. The pattern of changes is consistent with stress-related changes in the maturation of T and Treg cells, possibly due to changes in the immune synapse.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"4 ","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10256136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9625526","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":"MicroRNA profiling of the feline left heart identifies chamber-specific expression signatures in health and in advanced hypertrophic cardiomyopathy","authors":"Jessica Joshua ,&nbsp;Jeff L. Caswell ,&nbsp;Josep M. Monné Rodriguez ,&nbsp;Anja Kipar ,&nbsp;M. Lynne O'Sullivan ,&nbsp;Geoffrey Wood ,&nbsp;Sonja Fonfara","doi":"10.1016/j.jmccpl.2023.100037","DOIUrl":"10.1016/j.jmccpl.2023.100037","url":null,"abstract":"<div><p>Hypertrophic cardiomyopathy (HCM) is a common heart disease in humans and cats, nonetheless, the disease pathogenesis is still poorly understood. MicroRNAs are suspected to be involved in the disease process but the myocardial microRNA expression pattern in cats has not been identified. We hypothesized that microRNA profiles differ between healthy cats and cats with HCM. Small RNA sequencing on left ventricle (LV) and left atria (LA) samples from healthy cats (8 LV, 8 LA) and cats with HCM (7 LV, 5 LA) was performed. We identified 1039 differentially expressed microRNAs (False Discovery Rate &lt;0.01, fold change &gt;2). Cats with HCM were found to have a distinct microRNA expression profile with apparent regional heterogeneity. Comparing the HCM and control hearts, we detected 80 differentially expressed microRNAs for the HCM LV, and 37 for the LA. These included LV and LA enriched miR-21, miR-146b, and reduced miR-122-5p, which were recently suggested as key microRNAs for the HCM pathogenesis, and miR-132, which might be of therapeutic interest. Several top enriched microRNAs: miR-3958, miR-382-5p, miR-487a-5p (HCM LV); miR-chrD4_30107-3p (HCM LA); miR-3548 (HCM LV and LA) have either not been reported in the heart or only little is known. We identified potentially relevant microRNAs and further investigations into their role are required. Genes known to be targeted by the differentially expressed microRNAs were associated with inflammation and growth pathways in the HCM LV and LA, cardioprotective pathways in the LV, and fibrosis and structural changes in the LA when compared to healthy hearts.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"4 ","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41550996","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":"Mechano-energetic uncoupling in hypertrophic cardiomyopathy: Pathophysiological mechanisms and therapeutic opportunities","authors":"Vasco Sequeira ,&nbsp;Mark T. Waddingham ,&nbsp;Hirotsugu Tsuchimochi ,&nbsp;Christoph Maack ,&nbsp;James T. Pearson","doi":"10.1016/j.jmccpl.2023.100036","DOIUrl":"10.1016/j.jmccpl.2023.100036","url":null,"abstract":"<div><p>Hypertrophic cardiomyopathy (HCM) is a frequent inherited form of heart failure. The underlying cause of HCM is generally attributed to mutations in genes that encode for sarcomeric proteins, but the pathogenesis of the disease is also influenced by non-genetic factors, which can contribute to diastolic dysfunction and hypertrophic remodeling. Central to the pathogenesis of HCM is hypercontractility, a state that is an antecedent to several key derangements, including increased mitochondrial workload and oxidative stress. As a result, energy depletion and mechano-energetic uncoupling drive cardiac growth through signaling pathways such as ERK and/or potentially AMPK downregulation. Metabolic remodeling also occurs in HCM, characterized by decreased fatty acid oxidation and increased glucose uptake. In some instances, ketones may also feed the heart with energy and act as signaling molecules to reduce oxidative stress and hypertrophic signaling. In addition, arrhythmias are frequently triggered in HCM, resulting from the high Ca²⁺-buffering of the myofilaments and changes in the ATP/ADP ratio. Understanding the mechanisms driving the progression of HCM is critical to the development of effective therapeutic strategies. This paper presents evidence from both experimental and clinical studies that support the role of hypercontractility and cellular energy alterations in the progression of HCM towards heart failure and sudden cardiac death.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"4 ","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44442528","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":"Diet modification reverses diastolic dysfunction in rats with heart failure and preserved ejection fraction","authors":"Myung Yoon Kim ,&nbsp;Isabelle Pellot ,&nbsp;Catherine Bresee ,&nbsp;Asma Nawaz ,&nbsp;Mario Fournier ,&nbsp;Jae Hyung Cho ,&nbsp;Eugenio Cingolani","doi":"10.1016/j.jmccpl.2023.100031","DOIUrl":"10.1016/j.jmccpl.2023.100031","url":null,"abstract":"<div><p>Dahl Salt-Sensitive (DSS) rats develop heart failure with preserved ejection fraction (HFpEF) when fed a high-salt (8 % NaCl) diet. Hypertension-induced inflammation and subsequent ventricular fibrosis are believed to underlie the development of HFpEF. We investigated the role of diet modification in the progression of HFpEF using male DSS rats, fed either a high-salt diet from 7 weeks of age to induce HFpEF, or a normal-salt (0.3 % NaCl) diet as controls. After echocardiographic confirmation of diastolic dysfunction at 14–15 weeks of age along with HF manifestations, the HFpEF rats were randomly assigned to either continue a high-salt diet or switch to a normal-salt diet for an additional 4 weeks. HFpEF rats with diet modification showed improved diastolic function (reduced E/E′ ratio in echocardiogram), increased functional capacity (increased treadmill exercise distance), and reduced pulmonary congestions (lung/body weight ratio), compared to high-salt-fed HFpEF rats. Systolic blood pressure remained high (~200 mmHg), and ventricular hypertrophy remained unchanged. Ventricular arrhythmia inducibility (100 % inducible) and corrected QT interval (on ECG) did not change in HFpEF rats after diet modification. HFpEF rats with diet modification showed prolonged survival and reduced ventricular fibrosis (Masson's trichrome staining) compared to high-salt-fed HFpEF rats. Hence, the modification of diet (from high-salt to normal-salt diet) reversed HFpEF phenotypes without affecting blood pressure or ventricular hypertrophy.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"3 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10237345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9939338","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":"DEG (differentially expressed gene) or not DEG that is the question: Should we compare between datasets or not?","authors":"Ashutosh Tomar ,&nbsp;Samaneh Ekhteraei-Tousi ,&nbsp;H. Llewelyn Roderick","doi":"10.1016/j.jmccpl.2022.100029","DOIUrl":"10.1016/j.jmccpl.2022.100029","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"3 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47269317","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, quick off the blocks","authors":"Davor Pavlovic ,&nbsp;Rebekah Gundry","doi":"10.1016/j.jmccpl.2023.100032","DOIUrl":"10.1016/j.jmccpl.2023.100032","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"3 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43323194","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":"No cell fate conversion of macrophages to endothelial cells after myocardial infarction","authors":"Zhengkai Lu ,&nbsp;Lingfang Zhuang ,&nbsp;Ruiyan Zhang ,&nbsp;Kang Chen ,&nbsp;Hui Zhang ,&nbsp;Xiaoxiang Yan","doi":"10.1016/j.jmccpl.2022.100028","DOIUrl":"10.1016/j.jmccpl.2022.100028","url":null,"abstract":"","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"3 ","pages":"Article 100028"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45918143","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}