Cardiovascular Pathology最新文献

{"title":"Comparative investigation of Cx3cr1-Expressing Cardiac Macrophages in Atrioventricular Nodes of Wild-Type and Catecholaminergic Polymorphic Ventricular Tachycardia Mouse Model","authors":"Arzuhan Koc Buyuker ,&nbsp;Sumeyye Ozyaman ,&nbsp;Behnaz Karadogan ,&nbsp;Aylin Nebol ,&nbsp;Ilknur Keskin ,&nbsp;Esra Cagavi","doi":"10.1016/j.carpath.2025.107799","DOIUrl":"10.1016/j.carpath.2025.107799","url":null,"abstract":"<div><div>Cardiac macrophages were recently discovered to regulate cardiomyocyte function at the atrioventricular (AV) nodes of healthy murine and human hearts. Macrophages and immune mediators have been implicated in ischemia-induced cardiac damage and arrhythmia; however, the relevance of macrophages in congenital arrhythmia pathogenesis remains unclear. Here, the wild-type (WT) mice and <em>Calsequestrin2</em> gene null mutant (<em>Casq2^-/-</em>) transgenic model of catecholaminergic polymorphic ventricular tachycardia (CPVT) were comparatively evaluated for cardiac macrophage population at the histological level. The localization and density of the chemokine receptor, Cx3cr1-expressing cardiac macrophages were investigated <em>ex vivo</em> in heart sections from WT and <em>Casq2</em>^<em>-/-</em> mice at the AV node region using immunofluorescence, Masson’s Trichrome, and Hematoxylin-Eosin staining. Cx3cr1⁺ cardiac macrophages were localized in all cardiac layers and chambers of the heart, as well as septum and valve roots. Cx3cr1⁺ macrophages were coimmunostained and confirmed for expression of CD68 as a pan-macrophage marker. Macrophages were detected in close proximity to the cTnT⁺ cardiomyocytes in the myocardium of both WT and <em>Casq2</em>^<em>-/-</em> transgenic mice. Macrophage clusters were abundantly observed in the Hcn4 immunoreactive AV node region in healthy murine hearts. Subsequent quantification of signal intensities of Cx3cr1⁺ cardiac macrophages in the AV nodes in the <em>Casq2</em>^<em>-/-</em> transgenic mice was significantly lower than in WT mice. These results demonstrated a decline in Cx3cr1⁺ cardiac macrophages in AV node regions of CPVT mouse hearts, which could imply a potential contribution to arrhythmia. Our findings could serve as a valuable source for future functional investigations of macrophages in the pathogenesis of congenital arrhythmia.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"81 ","pages":"Article 107799"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562838","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":"Characterization of the clinical, histopathologic, and immunohistochemical features of large papillary fibroelastomas and their S100-expressing spindle cell component and its potential relationship to cardiac valvular interstitial cells","authors":"Faye Victoria C. Casimero ,&nbsp;James R. Stone","doi":"10.1016/j.carpath.2025.107800","DOIUrl":"10.1016/j.carpath.2025.107800","url":null,"abstract":"<div><div>Papillary fibroelastomas (PFEs) are uncommon, benign cardiac tumors most commonly measuring less than 1 cm and arising on cardiac valves. Large PFEs (≥1 cm), though clinically significant due to embolic potential, remain less well characterized. This study aimed to define the clinical, histopathologic, and immunohistochemical features of large PFEs, with a focus on the spindle cell component. A retrospective analysis was performed on 24 large PFEs resected between 2011 and 2024. Histologic analysis included hematoxylin and eosin staining, elastic staining, and immunohistochemistry for S100, calretinin, and CD31. The presence of a spindle cell component was defined as the presence of ≥10 non-surface spindle cells in a single 400x high-power field (HPF). S100⁺ spindle cells were quantified across 10 HPFs. Myxomatous mitral valves were also evaluated for comparison. Large PFEs were located in both cardiac chambers (n = 13) and on valves (n = 11). The median patient age was 69 years, and in all cases the tumor had been identified on imaging. Embolic events occurred in three (13%) of the cases, all from left-sided lesions. Seventeen (71%) of the large PFEs contained a spindle cell component, with significantly higher S100⁺ spindle cell density in valvular PFEs compared to chamber PFEs (median 14 vs. 1 per HPF; <em>P</em> = 0.045). In the large PFEs, CD31 was diffusely positive in surface endothelium, with variable endothelial S100 co-expression. There was only rare calretinin staining. The valvular interstitial cells in valves with myxomatous degeneration were also diffusely positive for S100. The presence of S100⁺ spindle cells in large PFEs suggests that a process similar to valvular interstitial cell activation and/or endothelial-to-mesenchymal transition may be important in PFE tumor pathogenesis.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"81 ","pages":"Article 107800"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562832","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":"Genetic mutations, pathology, and single-nucleus transcriptomic landscape in LVHT patients reveal differential progression to heart transplantation","authors":"Yifan Wang ,&nbsp;Weiteng Wang ,&nbsp;Han Mo,&nbsp;Xiumeng Hua,&nbsp;Hao Cui,&nbsp;Xiao Chen,&nbsp;Yue Zhang,&nbsp;Shun Liu,&nbsp;Yiqi Zhao,&nbsp;Jiangping Song","doi":"10.1016/j.carpath.2025.107808","DOIUrl":"10.1016/j.carpath.2025.107808","url":null,"abstract":"<div><h3>Background</h3><div>Left ventricular hypertrabeculation/non-compaction (LVHT/LVNC) is characterized by a thinned myocardial wall, prominent trabeculations, and deep intertrabecular recesses. It presents with unique cardiac morphology and hemodynamic features but displays considerable clinical heterogeneity. The factors influencing disease progression to heart transplantation remain unclear. No studies have investigated the relationship between transcriptomic or pathological features of LVHT and progression to transplantation.</div></div><div><h3>Methods</h3><div>We enrolled 74 patients diagnosed with LVHT, among whom 63 underwent whole-exome sequencing to assess genetic variants. Explanted heart tissue was obtained from 24 patients who received heart transplantation, and single-nucleus RNA sequencing was performed on the compacted and non-compacted layers of the left ventricle in 3 LVHT patients, compared with 3 normal controls. In addition, myocardial composition, fibrosis, fat content, and the extent of non-compaction were evaluated histopathologically.</div></div><div><h3>Results</h3><div>Genetic variants were detected in 46 % of patients but were not associated with progression to heart transplantation. The compacted and non-compacted layers of LVHT hearts exhibited highly similar transcriptional profiles. Notch signaling was enriched in LVHT-related cardiomyocyte clusters. <em>MAML3</em>, a Notch coactivator, was significantly upregulated in LVHT compared with other cardiomyopathies and normal myocardium, and was associated with faster progression to transplantation. Histopathological analysis further demonstrated that both myocardial fibrosis and the anatomical distribution of non-compaction were linked to cardiac function and transplant outcomes.</div></div><div><h3>Conclusion</h3><div>LVHT is associated with distinct transcriptomic and pathological features that influence the rate of progression to heart transplantation. The Notch pathway–related molecule <em>MAML3</em> may serve as a potential marker of disease progression in LVHT.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"81 ","pages":"Article 107808"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755469","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":"Corrigendum to “The mitochondrial uncoupler 2,4-dinitrophenol modulates inflammatory and oxidative responses in Trypanosoma cruzi -induced acute myocarditis in mice” [Cardiovascular Pathology 72 (2024) 107653]","authors":"José Edson Caetano-da-Silva ,&nbsp;Elda Gonçalves-Santos ,&nbsp;Elisa L.B.C. Domingues ,&nbsp;Ivo S. Caldas ,&nbsp;Graziela D.A. Lima ,&nbsp;Lívia F. Diniz ,&nbsp;Reggiani V. Gonçalves ,&nbsp;Rômulo D. Novaes","doi":"10.1016/j.carpath.2025.107806","DOIUrl":"10.1016/j.carpath.2025.107806","url":null,"abstract":"","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"81 ","pages":"Article 107806"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818105","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":"Mapping cardiac innervation in the long QT syndrome type 1 transgenic mouse model using whole heart imaging","authors":"Behnaz Forouhar Karadogan ,&nbsp;Aylin Karatas ,&nbsp;Esra Cagavi","doi":"10.1016/j.carpath.2025.107804","DOIUrl":"10.1016/j.carpath.2025.107804","url":null,"abstract":"<div><div>Cardiac innervation plays a crucial role in maintaining heart function. Abnormalities in cardiac innervation can be associated with arrhythmia, ischemic injury, and dysfunction, as documented in heart transplantation reports. There has been a lack of research on heart innervation patterns in congenital hereditary heart disease, including Long QT Syndrome (LQTS), which is a prevalent form of arrhythmia. By considering this gap, we comparatively analyzed global heart innervation patterns and axon fiber prevalence between wild-type (WT) and the <em>Kcnq1^A340E/A340E</em> mutation-bearing LQTS Type 1 transgenic mouse models. Hearts from WT and <em>Kcnq1^A340E/A340E</em> mice were immunostained with a pan-neuronal marker TUJ1 and imaged using the Lightsheet microscopy. The whole-heart images were processed and binarized to evaluate nerve fiber density, axon fiber diameter, focusing on fibers &lt; 2.5 μm and &gt; 2.5 μm on the dorsal and ventral sides of the heart, as well as branch number, length, and junction numbers. The comparative global innervation analysis of WT and <em>Kcnq1^A340E/A340E</em> transgenic mice hearts did not display a statistically significant difference in the TUJ1 immunoreactive nerve fiber density, analyzed by fluorescence intensity prevalence. Interestingly, the nerve fibers &lt; 2.5 μm were detected to have a lower prevalence in <em>Kcnq1^A340E/A340E</em> mice compared to WT mice on both dorsal and ventral sides. Furthermore, the branch number, branch length, or junction number of global heart innervation between the experimental groups showed similar quantitative values. Notably, the overlay of innervation patterns within and between WT and <em>Kcnq1^A340E/A340E</em> mice hearts revealed a distinct fiber distribution pattern. These findings indicated a unique, fingerprint-like innervation pattern in each heart, independent of the <em>Kcnq1</em> mutation. Collectively, our data indicated that the nerve fiber diameter distribution in the hearts of <em>Kcnq1^A340E/A340E</em> mice is slightly different from that of WT mice, and that there is a unique innervation pattern in each heart, similar to a heartprint, regardless of the mutation. Deciphering the underlying mechanisms behind ion channel mutations and cardiac innervation patterns by analyzing distinct congenital cardiac diseases awaits future investigation.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"81 ","pages":"Article 107804"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666438","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":"Spatial transcriptomics in the human left atrial appendage and pulmonary vein sleeve","authors":"Han Sun ,&nbsp;Juying Han ,&nbsp;Christine S. Moravec ,&nbsp;Toshihiro Okamoto ,&nbsp;Kenneth R. McCurry ,&nbsp;A. Marc Gillinov ,&nbsp;Mina K. Chung ,&nbsp;David R. Van Wagoner ,&nbsp;John Barnard ,&nbsp;Jonathan D. Smith","doi":"10.1016/j.carpath.2025.107802","DOIUrl":"10.1016/j.carpath.2025.107802","url":null,"abstract":"<div><div>Isolation of the pulmonary veins (PV) is a primary goal of ablation procedures to treat atrial fibrillation (AF), and the top genetic risk locus for AF is near PITX2, implicated in formation of the PVs. However, the challenges in obtaining PV tissues have limited progress in transcriptomic and mechanistic insights. Human PV and left atrial appendage (LAA) tissues, obtained from unused transplant donors, were used for spatial transcriptomic studies. Multiple cells and cell types may reside in each 55 µm diameter spatial area. Seurat clustering yielded 15 different clusters. Cell-type specific marker genes were used to determine the dominant cell types in these clusters, identifying several clusters enriched for cardiomyocytes, while others were enriched for additional cell types including fibroblasts, vascular smooth muscle cells, endothelial cells, and adipocytes. Spatial transcriptomics clearly resolved the venous, cardiomyocyte, and epicardial regions of the PV tissues, as well as fibrotic regions in LAAs and PVs. Spatial expression of the AF-associated genes <em>PITX2, SHOX2</em>, and <em>HCN4</em> confirmed presence in LAA and PVs with apparently higher expression of the cardiac master transcription factor <em>SHOX2</em> in the PV vs. LAA tissues, implicating the potential importance of <em>SHOX2</em> regulation in the PVs.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"81 ","pages":"Article 107802"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630196","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":"Usefulness of electron microscopy in the diagnosis of heterozygous Fabry disease with left ventricular outflow tract obstruction masquerading as hypertrophic cardiomyopathy","authors":"Hiromitsu Kanamori ,&nbsp;Tamami Yoshida ,&nbsp;Hideki Matsumoto ,&nbsp;Genki Naruse ,&nbsp;Shingo Minatoguchi ,&nbsp;Hiroyuki Okura","doi":"10.1016/j.carpath.2025.107809","DOIUrl":"10.1016/j.carpath.2025.107809","url":null,"abstract":"<div><div>Fabry disease, characterized by α-galactosidase A (GLA) deficiency, causes left ventricular hypertrophy (LVH) often mimicking hypertrophic cardiomyopathy (HCM). Differentiating Fabry disease from HCM is crucial, given their therapeutic and prognostic differences. A 42-year-old female diagnosed with HCM with left ventricular outflow tract (LVOT) obstruction was referred to our cardiology department after complaining of exertional chest discomfort. Electrocardiography showed LVH with strained ST segment. Echocardiography showed normal wall motion with asymmetric LVH and systolic anterior motion of the mitral valve with a basal LVOT resting gradient of 71 mmHg. Endomyocardial biopsy (EMB) revealed moderately vacuolated cardiomyocytes under light microscopy. Electron microscopy (EM) revealed abundant accumulation of lamellar bodies within cardiomyocytes. Although LVOT obstruction is common in HCM but rare in Fabry disease, the EMB findings suggested Fabry disease. Subsequent genetic testing identified a heterozygous p.Ala37Val (c.110C&gt;<em>T</em>) GLA variant (NM_000169.3), confirming the diagnosis. The patient was prescribed bisoprorol and cibenzorine, which improved her resting gradient and symptoms, and chaperon therapy was initiated. In this case, the patient’s symptoms mimicked HCM with no clinical evidence of Fabry disease other than the electron microscopic findings. This case highlights the importance of EMB using EM to exclude Fabry disease when asymmetric LVH is seen.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"81 ","pages":"Article 107809"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833174","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(26)00005-0","DOIUrl":"10.1016/S1054-8807(26)00005-0","url":null,"abstract":"","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"81 ","pages":"Article 107814"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920837","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":"Thoracic aortic diseases: Identification of diagnostic biomarkers using proteomic analysis","authors":"Nico Arndt ,&nbsp;Thomas Mair ,&nbsp;Maria Riedner ,&nbsp;Ali Biabani ,&nbsp;Hannah Voß ,&nbsp;Hartmut Schlüter ,&nbsp;Lukas Förster ,&nbsp;Tim Knochenhauer ,&nbsp;Marco Sachse ,&nbsp;Martin Beyer ,&nbsp;Maya Leonhardt ,&nbsp;Yskert von Kodolitsch ,&nbsp;Christian Schlein ,&nbsp;Guido Sauter ,&nbsp;Theresa Nauth ,&nbsp;Shiho Naito ,&nbsp;Evaldas Girdauskas ,&nbsp;Hermann Reichenspurner ,&nbsp;Christian Detter ,&nbsp;Georg Rosenberger ,&nbsp;Till Joscha Demal","doi":"10.1016/j.carpath.2025.107785","DOIUrl":"10.1016/j.carpath.2025.107785","url":null,"abstract":"<div><h3>Introduction</h3><div><strong>:</strong> Thoracic aortic aneurysms frequently go undetected until serious complications like acute dissections or ruptures arise. Therefore, this study aims to identify potential blood circulating biomarkers enabling an easy and early diagnosis of thoracic aortic disease.</div></div><div><h3>Methods</h3><div><strong>:</strong> Potential biomarker candidates were identified through two different techniques, untargeted and targeted proteomic as well as extracellular vesicle (EV) analyses. The biomarker levels were compared between two patient groups with thoracic aortic aneurysms and two control groups without thoracic aortic disease. In total, 80 patients (TAA group (<em>n</em> = 40) vs. control group (<em>n</em> = 40)) were matched for untargeted and targeted proteome analysis, and 85 for EV analysis (TAA group (<em>n</em> = 42) vs. control group (<em>n</em> = 43)), based on the availability of blood samples and excised aortic tissue. Levels of biomarker candidates were correlated with aortic diameter, patient age, and histological alterations in aortic tissue using linear and logistic regression models.</div></div><div><h3>Results</h3><div><strong>:</strong> The untargeted proteomic and EV analysis identified 1,037 and 1,077 proteins, respectively, of which 11 and 28 proteins showed significant differences in concentration between the study groups. Of these, 9 proteins correlated with the aortic diameter: ACTN1 (Regression coefficient <em>B</em> = 1.633, <em>p</em> &lt; 0.001), CRP (<em>B</em> = 0.001, <em>p</em> = 0.004), TGM3 (<em>B</em>=-0.293, <em>p</em> = 0.010), KRT84 (<em>B</em>=-0.477, <em>p</em> = 0.010), IGHG3 (-0.267, <em>p</em> = 0.018), DPYSL2 (<em>B</em> = 0.644, <em>p</em> = 0.020), TSPAN8 (B-0.838, <em>p</em> = 0.042), IGKV3D-11 (<em>B</em>=-0.242, <em>p</em> = 0.046), and VDAC1 (<em>B</em>=-0.491, <em>p</em> = 0.047). Moreover, IGKV3D-11 (<em>B</em>=-3.257, <em>p</em> = 0.029), IGHG3 (<em>B</em>=-0.003, <em>p</em> = 0.034), and APOC3 (<em>B</em>=-2.104, <em>p</em> = 0.037) showed significant correlations with the grade of aortic medial layer degeneration. None of the proteins correlated with patient age.</div></div><div><h3>Conclusion</h3><div><strong>:</strong> The study identified 9 biomarker candidates correlating with the aortic diameter. To enable the clinical use for diagnosis and prognostic assessment, these biomarkers need to be validated in larger external cohorts.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"80 ","pages":"Article 107785"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249875","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":"Quantified calcification in rat aortic valves isolated with the sinus of Valsalva coordinates with calciprotein particles formation","authors":"Shota Morikane ,&nbsp;Koichi Ishida ,&nbsp;Naoki Ashizawa ,&nbsp;Tetsuya Taniguchi ,&nbsp;Masaya Matsubayashi ,&nbsp;Naoki Kurita ,&nbsp;Seiichi Kobashi ,&nbsp;Takashi Iwanaga","doi":"10.1016/j.carpath.2025.107788","DOIUrl":"10.1016/j.carpath.2025.107788","url":null,"abstract":"<div><h3>Background</h3><div>Aortic valve sclerosis, in which calcification is a major pathogenesis, is a serious complication of chronic kidney disease. In small animal experiments, it is difficult to evaluate aortic valve calcification quantitatively except for diagnostic imaging because of their small size. In this study, to quantify rat aortic valve calcification, we isolated rat whole aortic valves and verified whether its calcification has own characteristics by investigating a relationship with calciprotein particles (CPP) formation, which is suggested as a biomarker of tissue calcification.</div></div><div><h3>Methods</h3><div>Human aortic valve interstitial cells (HAVICs) were cultured in a high-phosphate medium with or without two bisphosphonates, and their calcification was determined. The rats were injected with vitamin D to induce calcification and were treated with the bisphosphonates. The whole aortic valve was collected by trimming from the base of the aortic arch to the heart (including the sinus of Valsalva), and calcification and CPP formation in the serum were measured.</div></div><div><h3>Results</h3><div>Calcification of HAVICs was inhibited by two bisphosphonates accompanied by inhibition of CPP formation. In vitamin D-treated rats, calcium content of the region collected as aortic valve was equivalent to that of the aorta and higher than that of the heart, whereas calcification suppression by the bisphosphonates in the collected region was equivalent to that in the heart and stronger than that in the aorta. The bisphosphonate-induced inhibition percentages of calcification in the collected region correlated with that of CPP formation, and the correlation was different from that observed in the aorta and heart.</div></div><div><h3>Conclusions</h3><div>The collecting whole aortic valve allowed easy and accurate assessment of calcification, which was quantitatively supported by the close correlation with CPP formation, and showed different characteristic from those in the aorta and heart. The results will provide crucial information for exploring the mechanism of valve calcification and for the discovery of calcification inhibitors.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"80 ","pages":"Article 107788"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353954","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}