Cardiovascular Pathology最新文献

{"title":"Molecular features and cell composition of left-dominant arrhythmogenic cardiomyopathy reveals key pathways and therapeutic targets","authors":"Yiqi Zhao ,&nbsp;Mengda Xu ,&nbsp;Xiumeng Hua ,&nbsp;Yuan Chang ,&nbsp;Yixuan Sheng ,&nbsp;Dan Shan ,&nbsp;Ningning Zhang ,&nbsp;Xiao Chen ,&nbsp;Jiangping Song","doi":"10.1016/j.carpath.2025.107743","DOIUrl":"10.1016/j.carpath.2025.107743","url":null,"abstract":"<div><h3>Background</h3><div>Arrhythmogenic cardiomyopathy (ACM) is a myocardial disorder characterized by arrhythmias and an increased risk of sudden cardiac death, particularly in left-dominant arrhythmogenic cardiomyopathy (LACM), which primarily affects the left ventricle. This study aims to elucidate the cellular and molecular mechanisms underlying LACM by performing an in-depth single-nucleus RNA sequencing (snRNA-seq) analysis to identify key transcriptional signatures and pathways involved in the disease's pathogenesis.</div></div><div><h3>Method</h3><div>Human heart samples were collected from five patients undergoing heart transplantation due to ACM and from four healthy donors. Single nuclei were isolated from myocardial tissues and subjected to snRNA-seq using the 10 × Genomics Chromium platform. Data were processed and analyzed to identify distinct cell populations and their differentially expressed genes. Immunofluorescence staining was used to validate key findings.</div></div><div><h3>Result</h3><div>The snRNA-seq analysis revealed an increased proportion of fibroblasts and adipocytes in the left ventricles of LACM patients, suggesting a cellular basis for the fibrofatty remodeling observed in the disease. Key cell populations, including cardiomyocytes (CMs), fibroblasts (Fbs), and adipocytes (Adipo), were identified with distinct transcriptional profiles. We identified a disease-associated cardiomyocyte subpopulation (CM1) characterized by upregulation of fibrosis-, metabolism-, and stress-related markers, indicating transcriptional remodeling processes involved in LACM. The Fb subgroup Fb1 was characterized by genes involved in the PI3K-AKT signaling pathway. Adipocyte subpopulations exhibited gene expression features reflecting adaptation to the cardiac pathological environment, including markers associated with extracellular matrix remodeling and metabolic stress.</div><div>Immunofluorescence staining validated the high expression of key markers of LACM patients.</div></div><div><h3>Conclusion</h3><div>This study provides a cellular and molecular characterization of LACM, identifying key pathways and transcriptional signatures that contribute to the disease's pathogenesis. These findings enhance our understanding of LACM and offer potential targets for therapeutic intervention.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107743"},"PeriodicalIF":2.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVER 3: Editorial Board","authors":"","doi":"10.1016/S1054-8807(25)00025-0","DOIUrl":"10.1016/S1054-8807(25)00025-0","url":null,"abstract":"","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"77 ","pages":"Article 107740"},"PeriodicalIF":2.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVER 4: Table of Contents/Barcode PMS 200","authors":"","doi":"10.1016/S1054-8807(25)00026-2","DOIUrl":"10.1016/S1054-8807(25)00026-2","url":null,"abstract":"","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"77 ","pages":"Article 107741"},"PeriodicalIF":2.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-atherosclerosis effect and molecular mechanism of AMPKα1 by polarizing monocytes to an M2 phenotype via cell-intrinsic lysosomal lipolysis","authors":"Jing Wang ,&nbsp;Yahui Zhang ,&nbsp;Caixing Cao ,&nbsp;Jiale Hua ,&nbsp;Li Xing ,&nbsp;Changxin Wu","doi":"10.1016/j.carpath.2025.107742","DOIUrl":"10.1016/j.carpath.2025.107742","url":null,"abstract":"<div><div>Regulating the differentiation of monocytes into M2 macrophages can promote the regression of Atherosclerosis (AS) plaque. However, the key molecules regulating the differentiation of monocytes to M2 are unknown. In this study, we reported that adenosine-activated protein kinase α1 (AMPKα1) plays an anti-AS role by polarizing monocytes to an M2 phenotype via promoting fatty acid oxidation (FAO). AMPKα1 enhances the decomposition of cholesterol esters by increasing lysosomal acid lipase expression to provide fatty acids for FAO. Furthermore, AMPKα1 can induce lysosomal biogenesis and enhance lipolysis by promoting the transcription factor EB (TFEB) expression and facilitating TFEB nuclear translocation. In conclusion, AMPKα1 enhances the decomposition of cholesterol esters by increasing lysosomal acid lipase expression to produce fatty acids, which may represent a mechanism to promote FAO and inflammatory monocytes differentiation towards M2 phenotype.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107742"},"PeriodicalIF":2.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining “Vulnerable” in coronary artery disease: predisposing factors and preventive measures","authors":"Eleni Adamopoulou,&nbsp;Kyriakos Dimitriadis,&nbsp;Konstantinos Kyriakoulis,&nbsp;Nikolaos Pyrpyris,&nbsp;Eirini Beneki,&nbsp;Christos Fragkoulis,&nbsp;Dimitris Konstantinidis,&nbsp;Konstantinos Aznaouridis,&nbsp;Konstantinos Tsioufis","doi":"10.1016/j.carpath.2025.107736","DOIUrl":"10.1016/j.carpath.2025.107736","url":null,"abstract":"<div><div>The likelihood of a plaque to cause an acute coronary syndrome (ACS) depends on several factors, both lesion- and patient-related. One of the most investigated and established contributing factors is the presence of high-risk or “vulnerable plaque” characteristics, which have been correlated with increased incidence of major adverse cardiovascular events (MACE). The recognition, however, that a significant percentage of vulnerable plaques do not result in causing clinical events has led the scientific community towards the more multifaceted concept of “vulnerable patients”. Incorporating the morphological features of an atherosclerotic plaque into its hemodynamic surroundings can better predict the chance of its disruption, as altered fluid dynamics play a significant role in plaque destabilization. The advances in coronary imaging and the field of computational fluid dynamics (CFD) can contribute to develop more accurate lesion- and patient-related ACS prediction models that take into account both the morphology of a plaque and the forces applied upon it. The aim of this review is to provide the latest data regarding the aforementioned predictive factors as well as relevant preventive measures.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"77 ","pages":"Article 107736"},"PeriodicalIF":2.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal and demographic disparities in mortality trends for heart failure and COPD-associated heart failure in U.S. Adults: A 1999–2020 analysis of CDC WONDER data","authors":"Faizan Ahmed ,&nbsp;Tehmasp Rehman Mirza ,&nbsp;Sherif Eltawansy ,&nbsp;Zoha Khan ,&nbsp;Yusra Mashkoor ,&nbsp;Najam Gohar ,&nbsp;Hira Zahid ,&nbsp;Kainat Aman ,&nbsp;Zaima Afzaal ,&nbsp;Mushood Ahmed ,&nbsp;Hritvik Jain ,&nbsp;Aman Ullah ,&nbsp;Nisar Asmi ,&nbsp;Farman Ali ,&nbsp;Adnan Bhat ,&nbsp;Paweł Łajczak ,&nbsp;Ogechukwu Obi ,&nbsp;Muhammad Owais ,&nbsp;Naveen Baskaran","doi":"10.1016/j.carpath.2025.107735","DOIUrl":"10.1016/j.carpath.2025.107735","url":null,"abstract":"<div><h3>Background</h3><div>Heart failure (HF) carries varying mortality based on demographic distribution. Moreover, the interaction of HF with chronic obstructive pulmonary disease (COPD) raises this mortality. In this study, implementing national databases over a long time could assist in understanding mortality rates in patients suffering from two significant chronic diseases, HF and COPD.</div></div><div><h3>Methods</h3><div>This analysis utilized the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) system to assess the mortality trends between HF and COPD-associated HF in US adults aged 25–85+ from 1999 to 2020.</div></div><div><h3>Results</h3><div>This investigation detected a total of 6,755,700 deaths occurred in patients with HF in ages above 25. Fatalities of 1,141,819 (16.9 %) were associated with HF and comorbid COPD. Age-adjusted mortality Rates (AAMR) of HF-related deaths decreased from 162.7 to 154.4. (Average Annual Percentage Changes (AAPC): -0.49, 95 % CI: -0.63 to -0.34, <em>p</em> &lt; 000001, while the overall AAMR for HF with COPD among adults increased from 24.5 in 1999 to 28.2 in 2020. Men had significantly higher HF-related AAMRs and HF with comorbid COPD-related mortality than women. HF-related AAMRs were highest among NH Black or African Americans, followed by NH Whites. At the same time, on the other side, HF and COPD had the highest mortality in non-Hispanic (NH) White individuals, followed by NH Black individuals, then Hispanic individuals. Mortality in HF with COPD was the highest in the Northeast, then the Midwest, South, and least in the West states.</div></div><div><h3>Conclusion</h3><div>Implementation of a CDC database provided guidance over two decades about the US population mortality attributed to HF with and without the presence of COPD, which contributed to a better understanding of national trends in prevailing diseases with remarkable chronicity.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"77 ","pages":"Article 107735"},"PeriodicalIF":2.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The frequency of CD3+ lymphocytes in non-myocarditis endomyocardial biopsies","authors":"Marc K. Halushka ,&nbsp;Giulia d'Amati ,&nbsp;Melanie C. Bois ,&nbsp;Monica De Gaspari ,&nbsp;Carla Giordano ,&nbsp;Karin Klingel ,&nbsp;Charles Leduc ,&nbsp;Keiko Ohta-Ogo ,&nbsp;Ilke Ozcan ,&nbsp;Stefania Rizzo ,&nbsp;Celeste Santos-Martins ,&nbsp;Atsuko Seki ,&nbsp;Cristina Basso","doi":"10.1016/j.carpath.2025.107733","DOIUrl":"10.1016/j.carpath.2025.107733","url":null,"abstract":"<div><div>Lymphocytic myocarditis is a serious disease with significant morbidity and mortality. Cardiovascular pathology has an important role in its diagnosis, a diagnosis historically made using the presence of a lymphocytic infiltrate and myocyte injury (Dallas Criteria). The European Society of Cardiology (ESC) criteria, additionally, use a threshold of immune cells, determined by CD3 immunohistochemical stains to render the diagnosis of myocarditis on endomyocardial biopsy. However, the frequency of immune cells in non-myocarditis endomyocardial biopsy cases is unclear and dependent on different evaluation methods. Therefore, an international consortium of 6 centers assessed endomyocardial biopsies on patient populations for the count of CD3+ lymphocytes in the one busiest high-powered field (hpf) per case. In total, 359 biopsies, performed for reasons other than a clinical suspicion of myocarditis, were evaluated. The clinical decision to biopsy was mainly for the differential diagnosis of hypertrophic cardiomyopathy (<em>n</em> = 133, 37 %); amyloidosis (<em>n</em> = 103, 29 %); hypertensive heart disease (<em>n</em> = 96, 27 %) or other non-inflammatory diseases. The average number of CD3+ lymphocytes in the busiest hpf was 3.1 (median 2). Over 96 % of cases had fewer than 10 lymphocytes in the busiest hpf. There were no significant differences by sex or age, but institutional differences in the count of CD3+ lymphocytes were significant. These findings will help classify the abundance of lymphocytes on non-myocarditis endomyocardial biopsies for use in myocarditis criteria classifications.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"77 ","pages":"Article 107733"},"PeriodicalIF":2.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of moderate and high intensity endurance exercise on acute murine coxsackievirus B3 myocarditis","authors":"Manon Van Hecke ,&nbsp;Kasper Favere ,&nbsp;Sander Eens ,&nbsp;Matthias Bosman ,&nbsp;Peter L. Delputte ,&nbsp;Pieter-Jan Guns ,&nbsp;Tania Roskams ,&nbsp;Hein Heidbuchel","doi":"10.1016/j.carpath.2025.107734","DOIUrl":"10.1016/j.carpath.2025.107734","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and aims&lt;/h3&gt;&lt;div&gt;Myocarditis is a group of inflammatory diseases of the myocardium, with viral infections being the leading cause. Previous murine studies have demonstrated a detrimental effect of extensive exercise on the acute course of viral myocarditis. Recently, we were the first to report that continuation of moderate exercise during murine viral myocarditis modulates myocardial inflammation and fibrosis at the late stage of disease, yet we did not evaluate early time points. In this study, we aimed to evaluate the impact of moderate intensity training on the acute course of disease, and compare it to the effects of a high intensity protocol.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods and results&lt;/h3&gt;&lt;div&gt;Two separate experiments were performed. For the moderate intensity (Mod) endurance exercise experiment, 50 male C57BL/6J mice (11 weeks old) were randomised to 3 weeks of treadmill running (ModEEX, 18 cm/sec, daily) or not (ModSED). Two weeks into the experiment, animals received a single intraperitoneal injection with either coxsackievirus B3 (CVB) to induce viral myocarditis, or phosphate-buffered saline (PBS) vehicle. For the high intensity (Hi) endurance exercise experiment, another 20 male C57BL/6J mice (17 weeks old) were randomised to 3 weeks of treadmill running (HiEEX) or not (HiSED). After two weeks of training, all animals of the Hi experiment were injected with CVB, and the training protocol was intensified with increasing running speeds until exhaustion in the final week of training. All animals were sacrificed 6-7 days after virus or vehicle administration. All groups demonstrated complete survival except for 1 animal of the HiSED group, and showed comparable clinical signs and body weight evolution. Nor moderate, neither high intensity exercise had any significant impact on plasma troponin levels, semiquantitative scores of cardiomyocyte loss, and digital areas of necrosis. Morphologically however, HiEEX mice showed markedly less inflammatory cells in the necrotic areas of the myocardial lesions compared to HiSED mice, as was confirmed by digital quantification (x10&lt;sup&gt;3&lt;/sup&gt; inflammatory cells per mm&lt;sup&gt;2&lt;/sup&gt; HiEEX: 6.24±0.32SEM vs HiSED: 8.02 ±0.36SEM, P=0.002). The same digital quantification did not show significant differences between ModEEX and ModSED lesions. Using an extensive panel of immunohistochemical inflammatory cell markers, a different composition of inflammatory cell subtypes was observed in the myocardial lesions of HiEEX compared to ModEEX mice, with a shift towards a pro-inflammatory milieu in HiEEX mice (ratio iNOS/Arg1 HiEEX: 0.49 vs ModEEX: 0.22, P=0.041 and ratio Tbet/GATA3 HiEEX: 4.75 vs ModEEX: 0.82, P=0.005). The cardiac viral load varied considerably, but no impact of exercise was observed, nor did cardiac expression of remodelling genes (Serpina3n, CTGF, and TGF-β) show an exercise effect.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In the acute phase of murine viral myocarditis, lesions ","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"77 ","pages":"Article 107734"},"PeriodicalIF":2.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVER 3: Editorial Board","authors":"","doi":"10.1016/S1054-8807(25)00016-X","DOIUrl":"10.1016/S1054-8807(25)00016-X","url":null,"abstract":"","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"76 ","pages":"Article 107731"},"PeriodicalIF":2.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVER 4: Table of Contents/Barcode PMS 200","authors":"","doi":"10.1016/S1054-8807(25)00017-1","DOIUrl":"10.1016/S1054-8807(25)00017-1","url":null,"abstract":"","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"76 ","pages":"Article 107732"},"PeriodicalIF":2.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}