Cardiovascular Pathology最新文献

{"title":"Insights from autopsy-initiated pathological studies of the pathogenesis and clinical manifestations of atherosclerosis and ischemic heart disease: Part I. Atherosclerosis","authors":"L. Maximilian Buja ,&nbsp;Michelle M. McDonald ,&nbsp;Bihong Zhao ,&nbsp;Navneet Narula ,&nbsp;Jagat Narula ,&nbsp;Rolf F. Barth","doi":"10.1016/j.carpath.2025.107726","DOIUrl":"10.1016/j.carpath.2025.107726","url":null,"abstract":"<div><h3>Context</h3><div>Ischemic heart disease (IHD) due to coronary atherosclerosis constitutes the leading cause of morbidity and mortality worldwide. This review was undertaken to document the historical basis for our contemporary understanding of atherosclerosis-based disease and to provide a rationale for continued support for autopsy-based research to make further progress in reducing the morbidity and mortality from atherosclerosis-related disease.</div></div><div><h3>Objectives</h3><div>To analyze the contributions of the autopsy-initiated pathological studies to complement and validate other lines of investigation in determining the pathology and pathogenesis of the leading worldwide cause of morbidity and mortality, namely, atherosclerosis and its major complications of coronary atherosclerosis, ischemic heart disease, coronary thrombosis, acute myocardial infarction, and sudden cardiac death.</div></div><div><h3>Data sources</h3><div>Systematic search on PubMed to gather relevant studies concerning autopsy studies and reviews of the pathology and pathogenesis of atherosclerosis, ischemic heart disease, coronary atherosclerosis, coronary thrombosis, myocardial infarction, and sudden cardiac death</div></div><div><h3>Conclusions</h3><div>Extensive published reports have confirmed the continuing importance of the autopsy as a powerful tool to understand the pathogenesis, clinical features, and therapeutic options for major diseases. This specifically has been shown by the analysis of atherosclerosis and its major manifestation of ischemic heart disease, as presented in this (Part I) and its companion (Part II) review. Autopsy-initiated pathological studies have documented the prevalence and natural history of atherosclerosis in different human populations in relationship to the prevalence of risk factors and established that the clinically silent phase of the disease begins in the first decades of life. Insights from these studies have been essential in developing and evaluating strategies for continued progress in preventing and controlling the disability and death associated with atherosclerotic heart disease.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"76 ","pages":"Article 107726"},"PeriodicalIF":2.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456995","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":"Mitral Isthmus anatomy: Detailed examination and classification proposal","authors":"Buse Naz Çandır Gürses ,&nbsp;Kader Yılar ,&nbsp;Çağla Ergin ,&nbsp;Özcan Gayretli","doi":"10.1016/j.carpath.2025.107723","DOIUrl":"10.1016/j.carpath.2025.107723","url":null,"abstract":"<div><h3>Aim</h3><div>The aim of this study was to investigate the anatomical features of the mitral isthmus (MI) line, the vessels located there and their localisation in the MI line.</div></div><div><h3>Methods</h3><div>MI length and wall thickness were measured in a total of 65 autopsied fresh hearts. The distances of the vessels at the level of MI to the left inferior pulmonary vein (LIPV), mitral annulus (MA), endocardium surface (ES) and lateral adipose tissue (LAT) were recorded.</div></div><div><h3>Results</h3><div>The mean linear length of MI and left atrial wall thickness were 49.6 ± 9.9 mm and 3.9 ± 1.2 mm, respectively. GCV and LCx are approximately 1 cm from MA, 4 cm from LIPV, 5-6 mm from ES and 7 mm from LAT. Great cardiac vein (GCV) was found to be located in the MI line in 100 %, left circumflex artery (LCx) in 60 %, and vein of Marshall (VOM) in 63.1 % of cases. Presence of only GCV was recorded as Type-1 (18.5 %), GCV and LCx as Type-2 (18.5 %), GCV and VOM as Type-3 (21.5 %) and presence of all three as Type-4 (41.5 %). LCx located below the GCV was recorded as Type-A (59 %), above the GCV as Type-B (25.6 %), and at the same level but with LCx on the endocardial surface as Type-C1 (12.8 %) and on the epicardial surface as Type-C2 (2.6 %).</div></div><div><h3>Conclusion</h3><div>This study proves that the anatomy of MI is far from standardised and helps to raise awareness of the vascular pattern that may be encountered prior to ablation intervention.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"76 ","pages":"Article 107723"},"PeriodicalIF":2.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073978","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":"Seasonal variation of unexpected sudden cardiac death in northern Finland","authors":"Severi M Mattila ,&nbsp;Hanna Latola ,&nbsp;Lasse Pakanen ,&nbsp;Jenni J Hekkanen ,&nbsp;M Anette E Eskuri ,&nbsp;Juha Vähätalo ,&nbsp;Olavi H Ukkola ,&nbsp;M Juhani Junttila ,&nbsp;Heikki V Huikuri ,&nbsp;Juha S Perkiömäki","doi":"10.1016/j.carpath.2025.107725","DOIUrl":"10.1016/j.carpath.2025.107725","url":null,"abstract":"<div><h3>Background</h3><div>Data on the occurrence of unexpected sudden cardiac death (SCD) in different seasons are limited.</div></div><div><h3>Methods</h3><div>All unexpected sudden death victims have to undergo medico-legal autopsy obligated by the Finnish law. Consecutive series of all unexpected autopsied SCD victims (n = 5,869) were prospectively collected from the geographically defined area in the Northern Finland during a twenty years period from 1998 to 2017. We evaluated the seasonal variation of SCD and its possible causes.</div></div><div><h3>Results</h3><div>Unexpected SCD occurred more frequently during the first quarter of a year (from January to March) than during the other quarters. The occurrence of SCD during the twenty years follow-up was 4.5 ± 0.24 during the first quarter of the year per month and 3.9 ± 0.12 during the other quarters of the year per month on average (SCDs during the quarter of a year per month on average per 100,000 inhabitants per year, p &lt; 0.001). The weather was colder during the first quarter of the year (average temperature -9.1 degrees centigrade) than during the other quarters (average temperature +5.7 degrees centigrade). The subjects who experienced SCD during the first quarter of the year had more commonly severe (75 %-90 %) coronary artery stenosis, (p &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Unexpected SCD occurred more commonly during the first quarter of a year (from January to March) than during the other quarters (from April to December). Cold weather with its physiological consequences and more severe coronary artery disease predisposing to ischemia may have contributed to the increased occurrence of SCD during the first quarter of the year.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"76 ","pages":"Article 107725"},"PeriodicalIF":2.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063838","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":"Intimal sarcoma of the lower pulmonary vein diagnosed by Endobronchial Ultrasound-Guided Fine-Needle Aspiration (EBUS-FNA): A case report and comprehensive literature review","authors":"H. Elmas ,&nbsp;I. Kholová ,&nbsp;S. Meierling ,&nbsp;L. Welker","doi":"10.1016/j.carpath.2025.107717","DOIUrl":"10.1016/j.carpath.2025.107717","url":null,"abstract":"<div><div>Intimal sarcoma of blood vessels is a rare, aggressive tumor originating from vascular endothelial cells. This report presents a 22-year-old male diagnosed with an intimal sarcoma of the lower pulmonary vein, detailing diagnosis, treatment, and prognosis information. Additionally, this report explores the application application of Endobronchial Ultrasound-Guided Fine-Needle Aspiration (EBUS-FNA) alongside with Rapid Remote Online Evaluation (ROLE) for identifying a mass-like lesion in the pulmonary vein. We emphasize the value of this technique for supporting ancillary studies like immunohistochemistry. The importance of accurate diagnostic methods and personalized treatment management to improve prognosis in rare cancers is highlighted by this thorough analysis.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"76 ","pages":"Article 107717"},"PeriodicalIF":2.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000885","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":"An autopsy case of TFE3-rearranged PEComa-like neoplasm with systematic embolization involving the heart","authors":"Ikoi Omatsu ,&nbsp;Hiroki Mukai ,&nbsp;Toshifumi Doi ,&nbsp;Takeshi Ishikawa ,&nbsp;Yoshito Itoh ,&nbsp;Eiichi Konishi ,&nbsp;Yukiko Shishido-Hara","doi":"10.1016/j.carpath.2025.107715","DOIUrl":"10.1016/j.carpath.2025.107715","url":null,"abstract":"<div><div>A rare autopsy case of malignant <em>transcription factor E3</em> (<em>TFE3</em>)-rearranged perivascular epithelioid cell tumor (PEComa)-like neoplasm is presented. An 84-year-old woman manifested multiple cerebral infarctions and repetitive embolic events in the supra mesenchymal artery (SMA), and the presence of a mobile mass in the heart's left ventricle was also revealed. Tumoral lesions were also found in a pelvic space and a right pleural cavity, and a biopsy was performed from one of the disseminated tumor masses in the right pleura. Pathological diagnosis of <em>TFE3</em>-rearranged PEComa-like neoplasm was defined based on the evidence of partial expression of Melan A, and strong nuclear expression of TFE3 and by detection of the Xp11.2 locus split signal with FISH. A post-mortem analysis via autopsy revealed the widespread intravascular tumors in the heart's left ventricle, supra mesenchymal vein (SMV), and partial vein. The left intraventricular tumoral mass was associated with thrombus and fibrine, and thrombotic emboli were also found in SMA, SMV, and left pulmonary arteries. Interestingly, organ-based tumor invasion accompanying desmoplastic reactions was hardly seen. The small intestine was perforated, likely due to ischemia, which resulted in suppurative peritonitis and sepsis. This was thought of as the direct cause of death.</div><div>This is the first report of a precise autopsy investigation of <em>TFE3</em>-rearranged PEComa-like neoplasm. Tumoral localization was mostly intravascular or disseminative in the pleural cavity. Given the limited understanding of this tumoral pathophysiology, this case offers valuable insights for prompt diagnosis and effective treatment strategies.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"75 ","pages":"Article 107715"},"PeriodicalIF":2.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963758","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":"Mast cells and arteriogenesis: A systematic review","authors":"Alice Nassar ,&nbsp;Elizabeth Wagura ,&nbsp;Marios Loukas","doi":"10.1016/j.carpath.2025.107716","DOIUrl":"10.1016/j.carpath.2025.107716","url":null,"abstract":"<div><div>Vascular occlusive diseases remain a major health burden worldwide, necessitating a deeper understanding of the adaptive responses that mitigate their impact. Arteriogenesis, the growth and remodeling of collateral vessels in response to arterial occlusion, is a vital defense mechanism that counteracts fluid shear stress-induced vascular stenosis or occlusion. While physical factors driving arteriogenesis have been extensively studied, the specific cellular mediators involved are poorly understood. Notably, the role of innate and adaptive immune cells, particularly mast cells, in arteriogenesis has received limited attention. This systematic review bridges this knowledge gap by investigating the contribution of mast cells to vascular cell proliferation and leukocyte recruitment in arteriogenesis. A comprehensive search of major databases using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines reveals the critical connection between mast cells, inflammatory cells, innate immune cells, and growth factors in arteriogenesis. Our findings highlight the molecular mechanisms of mast cell activation, sheer stress exertion, and pro-arteriogenic growth factor recruitment. Furthermore, we explore the endogenous and exogenous factors, including nitrite, dipyridamole, thrombin, and cobra venom, triggering mast cell-mediated release of pro-arteriogenic factors. Additionally, we examine the impact of recombinant parathyroid hormone (rPTH) therapy on mast cell numbers and arteriogenesis in bone defect and allograft healing. Our review provides compelling evidence for the pro-arteriogenic role of mast cells, particularly during the early inflammatory phase of vessel occlusion, suggesting that targeting mast cell activation may be a promising therapeutic strategy for enhancing arteriogenesis and treating ischemia-related diseases.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"75 ","pages":"Article 107716"},"PeriodicalIF":2.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945104","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":"Sudden death in a case of triple-vessel, non-atherosclerotic, diffuse ectasia and aneurysmal dilatations of the coronary arteries: An autopsy report","authors":"Shatishraj Jothee ,&nbsp;Zhao Peng Koo ,&nbsp;Mary N. Sheppard ,&nbsp;Tuan Minanoriah binti Tuan Muda","doi":"10.1016/j.carpath.2024.107714","DOIUrl":"10.1016/j.carpath.2024.107714","url":null,"abstract":"<div><div>Aneurysmal Coronary Artery Disease (ACAD) can occur as localized dilations of a segment of one or more coronary arteries or diffuse ectasia-type dilatations of one or more coronaries. Atherosclerosis remains the most common cause of these aneurysms, with Kawasaki Disease being implicated in the Asian population. We present a case of a 62-year-old Asian woman who dies suddenly with no prior symptoms. and underwent an autopsy. Her heart showed diffuse aneurysmal dilatations of the epicardial coronary arteries, with a giant saccular aneurysm of the left main coronary artery. Histopathology revealed medial degeneration of the aneurysmal wall with no evidence of atheroma or vasculitis. Following a review of the pathological causes of coronary aneurysms, it is likely that the cause of such diffuse dilatations of the coronaries could be previous vasculitis such as Kawasaki disease.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"75 ","pages":"Article 107714"},"PeriodicalIF":2.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926595","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":"Rapid versus slow degeneration and complications of biomaterials in patients with congenital heart disease","authors":"Armin Darius Peivandi ,&nbsp;Michael Holtkamp ,&nbsp;Hennes Rave ,&nbsp;Lars Linsen ,&nbsp;Sven Martens ,&nbsp;Klaus-Michael Müller ,&nbsp;Uwe Karst ,&nbsp;Sabrina Martens","doi":"10.1016/j.carpath.2024.107712","DOIUrl":"10.1016/j.carpath.2024.107712","url":null,"abstract":"<div><h3>Objectives</h3><div>Re-operations due to material degeneration carry a burden for patients with congenital heart disease (CHD). The study aim was to compare rapid vs. slow degeneration of biomaterials in CHD patients.</div></div><div><h3>Methods</h3><div>Explants from re-operations of 29 CHD patients (2015-2022) were grouped according to the duration of implantation (short implantation &lt; 3 years (n = 16) vs. long implantation 10-15 years (n = 13)). Histologic processing and staining allowed tissue and calcification analysis. Micro-X-ray fluorescence (µXRF) was used for elemental analysis. Semi-quantitative comparison of calcium was conducted using a self-developed software.</div></div><div><h3>Results</h3><div>Thrombosis was recurrently observed in short-implanted RVOT samples. 62.5 % (n = 10) of short-implanted samples showed calcification in Alizarin red staining, in comparison to 69.2 % (n = 9) in the long-implanted group. µXRF analysis revealed calcium deposits in all patients, mostly co-localized with phosphorus. In the short implant group, other detected elements included iron, chlorine, chromium, nickel, titanium and zinc. In the long implant group, iron, nickel, titanium, zinc, copper and iodine were found. No significant difference in calcification (Ca-Si-ratio) between both implantation groups (p = 0.083) was found.</div></div><div><h3>Conclusion</h3><div>Thrombus formation is a main rapid degeneration cause in the RVOT. Deteriorations of biomaterials in CHD patients show strong parallels to bioprosthetic valve degenerations. Early calcification in young patients is supported by our semi-quantitative calcium analysis. The role of other elements in graft degeneration remains to be assessed in the future.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"75 ","pages":"Article 107712"},"PeriodicalIF":2.3,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920792","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":"Relationship between myocardial fibrosis and left bundle branch block. Does it exist?","authors":"Elena Rimskaya ,&nbsp;Olga Aparina ,&nbsp;Olga Stukalova ,&nbsp;Semen Kormilitsyn ,&nbsp;Nataliia Mironova ,&nbsp;Petr Chumachenko ,&nbsp;Sergey Ternovoy ,&nbsp;Sergey Golitsyn","doi":"10.1016/j.carpath.2024.107713","DOIUrl":"10.1016/j.carpath.2024.107713","url":null,"abstract":"<div><h3>Aim</h3><div>to assess the relation of focal and diffuse left ventricular (LV) fibrosis to left bundle branch block (LBBB).</div></div><div><h3>Materials and methods</h3><div>60 patients with dilated cardiomyopathy and LBBB (DCM-LBBB), 50 DCM-nonLBBB patients, 15 patients with LBBB and structurally normal heart (idiopathic LBBB) and 10 healthy volunteers (HV) underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). LGE LV images were post-proceeded for core scar (CS) and gray zone (GZ) calculation. Diffuse LV fibrosis was estimated on LGE-CMR images with the diffuse intensity ratio (DIR). Endomyocardial biopsy (EMB) was performed in 15(24.6 %) DCM-LBBB and 16 (32 %) non-LBBB DCM patients and allowed the quantification of collagen volume fraction (CVF).</div></div><div><h3>Results</h3><div>The percentage of CVF correlated with the DIR value in the same segment (<em>r</em> = 0.66, <em>p</em> &lt; 0.001). The value of CVF in EMB and frequency of LGE in both DCM groups was comparable (<em>p</em> = 0.8). In DCM-nonLBBB patients the percentage of CS was significantly higher (4.0[1.6; 11.7]% versus 1.4[0.1;8.5]% in DCM-LBBB patients, <em>p</em> = 0.047), whereas percentage of GZ and total fibrosis in both DCM groups was comparable. DIR value was higher in patients with idiopathic LBBB than in HV (0.54±0.09 versus 0.34±0.1, р&lt;0,001).</div></div><div><h3>Conclusion</h3><div>Neither focal nor interstitial fibrosis is associated with LBBB in DCM patients. Diffuse inflammation in DCM-LBBB patients may contribute to the progression of systolic dysfunction but is not a cause of LBBB. The increased value of interstitial fibrosis in patients with idiopathic LBBB may reflect latent diffuse process in myocardium inexorably leading to DCM development.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"75 ","pages":"Article 107713"},"PeriodicalIF":2.3,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920800","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":"Tocilizumab does not ameliorate inflammation-induced left ventricular dysfunction in a collagen-induced arthritis rat model","authors":"Ashmeetha Manilall ,&nbsp;Lebogang Mokotedi ,&nbsp;Sulè Gunter ,&nbsp;Regina Le Roux ,&nbsp;Serena Fourie ,&nbsp;Aletta ME Millen","doi":"10.1016/j.carpath.2024.107711","DOIUrl":"10.1016/j.carpath.2024.107711","url":null,"abstract":"<div><h3>Background</h3><div>Interleukin-6 (IL-6) is an attractive therapeutic target due to its diverse roles in the pathogenesis of conditions characterized by systemic inflammation. IL-6 has also been implicated in the pathophysiology of heart failure. This study aimed to investigate the impact of IL-6 receptor blockade with tocilizumab on the molecular pathways underlying systemic inflammation-induced left ventricular (LV) dysfunction in a collagen-induced arthritis (CIA) rat model.</div></div><div><h3>Methods</h3><div>Seventy-three Sprague-Dawley rats were divided into three groups: control (n=28), CIA (n=29), and CIA+IL-6 blocker (n=16). Inflammation was induced in the CIA and CIA+IL-6 blocker groups using bovine type II collagen emulsified in incomplete Freund's adjuvant. After arthritis onset, the CIA+IL-6 blocker group received tocilizumab for six weeks. Circulating inflammatory markers, relative LV mRNA gene expressions, and LV systolic and diastolic function were assessed.</div></div><div><h3>Results</h3><div>CIA rats developed LV diastolic and early-stage LV systolic dysfunction, which was not ameliorated by IL-6 blocker administration (<em>p</em> &gt; 0.05). IL-6 blocker administration did not impact circulating inflammatory markers (all <em>p</em> &gt; 0.05) or LV mRNA expression of inflammatory markers compared to the CIA group, nor did it reverse inflammation-induced increases in LV mRNA expression of genes involved in fibrosis and collagen turnover, regulation of titin phosphorylation, Ca²⁺ handling, mitochondrial function, or apoptosis (all <em>p</em> &gt; 0.05). However, LV mRNA expressions of <em>CD68</em> and <em>LOX</em>, genes involved in macrophage infiltration and collagen cross-linking, were increased in the CIA group (<em>p</em> = 0.03, <em>p</em> = 0.0004), but not in the CIA+IL-6 blocker group compared to controls (<em>p</em> &gt; 0.05).</div></div><div><h3>Conclusion</h3><div>These results suggest that although IL-6 blockade by tocilizumab may prevent inflammation-induced collagen cross-linking, the current treatment regimen may not protect against inflammation-induced LV dysfunction. Therefore, the role of IL-6 in the molecular mechanisms of inflammation-induced LV dysfunction remains inconclusive.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"75 ","pages":"Article 107711"},"PeriodicalIF":2.3,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902581","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}