ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 post-transplantation year. Analysis of 1st year’s rejection prob- ability resulted in 95% confidence interval (CI) of Grade 0 – 52.9% through 79.1% compared to 2nd year of 95% CI [63.6%; 76.4%] and 3rd year of 95% CI [45.9%; 61.7%] with decrease of Grade 0 EMBs in 3rd year. Conclusion: Tendencies of no rejection or mild ACR in EMBs suggest that long-term surveillance is irreplaceable tool for effective clinical observation of probable progress of cardiac allograft’s injuries. These tendencies detected in study may strongly suggest that procedures of cardiac allograft’s pathology testing for transplanted-heart patients are properly prescribed for those patients who demonstrate features of rejection over the years, and 95% CI calculated in this research is a safe indicator that nowadays prescribed EMBs are effectively indicated in risk patients. PS-19-004 Primary heart tumours, a single-centre, and 11 years of experience E.B. Balaban*, M. Çıkrıkçıoğlu, H. Kuplay, F. Aker *Haydarpasa Numune Training and Research Hospital, Department of Pathology, Turkey Background & objectives: In this study, clinicopathological features and follow-up data of 80 primary cardiac tumours diagnosed between 2011-2022 were evaluated. Methods: The study was a retrospective review of 77 patients. Results: Of the 77 cases (F/M: 49/28) included in the evaluation, 70 (90.9%) were benign, and 7 (9.1%) were malignant. The mean age at surgery was 53 in benign, and 36 in malignant cases. 60 (86%) of the benign tumours were myxomas. Benign tumours other than myxoma consisted of 5 papillary fibroelastomas, 2 haemangiomas, 1 lipoma, 1 hamartoma, 1 rhabdomyoma. Malignant tumours consisted of 2 spindle cell pleomorphic sarcoma, 2 embryonal rhabdomyosarcoma, 1 angiosarcoma, 1 synovial sarcoma, and 1 myxofibrosarcoma. The follow-up period was 6-140 months in benign cases, 8-56 months in malignant cases. During this period only 5 of the malignant cases died. Mean survival in malignant cases was 21 months. Conclusion: Surgical resection is the first treatment option for pri- mary cardiac tumours. Histopathological diagnosis of the tumour plays a fundamental role in guiding further follow-up and treat- ment. While it can be achieved nearly 100% survival with surgi- cal resection in benign cases, the results are not satisfactory in malignant cases. PS-19-005 Stereological estimation of myocardial fat and its relation to obesity, epicardial and visceral adipose tissue P. Holm*, L. Hindsø, K.B. Olsen, J. Banner *Institute of Forensic Medicine, Denmark Background & objectives: The normal heart includes epicardial adipose tissue (EAT) and myocardial fat – both increase with obesity. EAT is related to risk of heart disease and myocardial fat with arrhythmogenesis. The objectives is to estimate myocardial fat using stereological methods. Methods: We included 115 deceased with a post-mortem com- puted-tomography of the eviscerated heart to establish EAT vol- ume. We examined six samples (ant., lat., and post.) from the left (LV) and right ventricle (RV) of the midventricular slice. The percentage of myocardial fat was estimated stereological using Visiopharm software. Kidney and omental fat were weighed at autopsy and waist-hip-ratio calculated. Results: The group consisted of more males (66/49; 57%), mean age at death was 53.4 years (range 21-93) and mean BMI was 25.4 (±5.6). Females had a slightly non-significant (p=0.054) larger proportion of RV fat (mean 12.1%, range 9.7-16.6) compared to men (10.8%, range 9.4-12.8). We found a positive correlation with BMI and LV fat (p=0.033). In the RV the correlation was only borderline significant (p=0.052). EAT volume was positively cor- related with fat in the RV and LV. We found no association with waist-hip-ratio, omental or kidney fat as measures of visceral adi- pose tissue (VAT). Conclusion: Myocardial fat is a normal component especially in the RV and correlates with the total volume of EAT. We surpris- ingly found no association with VAT. PS-19-006 SET7 methyltransferase mediates the up-regulation of NADPH oxidase expression and oxidative stress in the atherosclerotic aorta of apolipoprotein E-deficient mice A. Manea*, M.L. Vlad, A. Lazar, S. Manea *Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Romania Background & objectives: Histone methylation-related epigenetic pathways emerged as promising therapeutic targets in atherosclerosis. The study aimed at investigating the functional implication of SET7 in the regulation of NADPH oxidase (Nox) expression, an important source of oxidative stress in experimental atherosclerosis. Methods: Human non-atherosclerotic and atherosclerotic tissue specimens, apolipoprotein E-deficient (ApoE-/-) mice, and polar- ized pro-inflammatory (M1) and anti-inflammatory (M2) mouse macrophages (Mac) were investigated employing real-time PCR, Western blot, and microscopy. Male ApoE-/- mice fed a normal or a high-fat, cholesterol-rich diet (HD) were randomized to receive 5 mg/kg (R)-PFI 2 hydrochloride, a selective SET7 inhibitor, or its vehicle for 4 weeks. Results: Pharmacological inhibition of SET7 had no signifi- cant effects on plasma total cholesterol, triglycerides, and body weights as compared with vehicle-treated ApoE-/- (HD) animals. The mRNA and protein levels of SET7 were found significantly elevated in human atherosclerotic lesions, atherosclerotic aorta of ApoE-/- (HD) mice, and in M1-Mac. Inhibition of SET7 suppressed the up-regulation of Nox1, Nox2, and Nox4 subtypes in the aorta of ApoE-/- (HD) mice and in M1-Mac. Treatment of ApoE-/- (HD) mice with SET7 inhibitor reduced significantly the aortic forma- tion of 4-hydroxynonenale-/nitrotyrosine-protein adducts (impor- tant markers of oxidative stress). Significant increases in Nox1, Nox2, Nox4, Nox5, and p22phox transcript levels were detected in HEK293 reporter cells overexpressing SET7. Conclusion: SET7 is a key epigenetic enzyme that methylates nucleosomal histones (H3) and non-histone proteins (transcrip- tion factors) at different lysine residues to regulate the expression of the target genes. The novel data of this study indicate that SET7 methyltransferase is up-regulated in human atherosclerosis and mediates NADPH oxidase up-regulation and oxidative stress in experimental atherosclerosis. Pharmacological targeting of SET7 methyltransferase could become an important supportive therapeu- tic strategy in atherosclerosis. Funding: Work supported by UEFISCDI (PN-III-P4-ID- PCE-2020-1898, PN-III-P1-1.1-TE-2021-0180, PN-III-P2-2.1- PED-2019-2497, PN-III-P2-2.1-PED-2019-2512). S157