Increased somatic mosaicism in autosomal and X chromosomes for suicide death.

Mosaic chromosomal alterations (mCAs) are classified as mosaic deletions (loss), copy-neutral loss of heterozygosity (CN-LOH), and duplications (gain), attracting special attention as biological aging-related acquired genetic alterations. While these mCAs have been linked with aging and various diseases, no study has investigated their association with suicide risk which is associated with abnormal biological aging. Here, we examined the association between suicide deaths and mCAs, including mosaic loss of the X (mLOX) and Y chromosomes, by leveraging blood-derived single nucleotide polymorphism-array data. The first (410 suicide decedents and 88,870 controls) and the second (363 suicide decedents and 88,870 controls) cohorts were analyzed and integrated using meta-analyses (773 suicide decedents and 177,740 controls). Total mCAs in autosomal chromosomes were significantly increased in suicide (p = 1.28 × 10-6, odds ratio [OR] = 1.78), mostly driven by loss (p = 4.05 × 10-9, OR = 2.70) and gain (p = 1.08 × 10-3, OR = 2.23). mLOX were significantly increased in female suicide (p = 2.66 × 10-21, OR = 4.00). The directions of effects of all mCAs in autosomal and sex chromosomes on suicide were the same in the first and second sets. Subgroup analyses suggest that our findings were mostly driven by suicide itself, and not confounded by comorbid psychiatric disorders or physical diseases, smoking status, sample location, or postmortem sample status. In conclusion, we provide the first evidence for aberrant mCAs in somatic autosomal and X chromosomes in suicide, which may contribute to an improved understanding of the genomic pathophysiology underlying suicide.

An Autopsy Case Report of Homicide by Methanol Intoxication With Pinkish Bilateral Putamina.

ABSTRACT: Many deaths caused by methanol occur as a result of intentional suicide attempts or accidental ingestion, and several investigators have quantified methanol and formic acid in blood and organs. However, to the best of our knowledge, no reports have described regional differences in the concentration of methanol in the brain. A man in his 50s drank alcohol that had been deliberately contaminated with methanol by his wife, and he died of multiple-organ failure after 4 days of intensive medical treatment including hemodialysis. On medicolegal autopsy, cross sections of the brain showed scattered petechial hemorrhage in the brain stem and microscopic hemorrhage with congestion in the bilateral putamina, which showed pinkish discoloration. The concentrations of methanol, formic acid, and ethanol in autopsy samples were measured by headspace gas chromatography, revealing relatively high concentrations of residual methanol and formic acid in the brain (especially in the basal ganglia), although methanol had been eliminated from the blood. Even after 4 days of medical treatment, postmortem toxicological analysis of the brain tissue indicated methanol ingestion. The accumulation of formic acid and the consequent local metabolic acidosis may cause brain lesions.

Blunt traumatic aortic dissection death by falling: an autopsy case report.

A man in his early 60 s who worked at a waste disposal plant had fallen into the refuse pit and was immediately taken to the emergency department for treatment. After 8 days without recovering consciousness, the man died. Antemortem contrast-enhanced computed tomography at the emergency department indicated Stanford type B/DeBakey type IIIb aortic dissection. The autopsy showed a sharp and transverse intimal tear 0.6 cm in length in the aortic isthmus and fractures in the 5th-6th thoracic vertebrae. No structural abnormalities in arterial walls were noted on histopathological examination. The traumatic aortic dissection induced by falling is rare, compared with vehicle crash. Although the verification process was challenging, the cause of death was ultimately concluded as traumatic aortic dissection due to falling into the refuse pit. The following observations were cited as evidence: (1) the location and feature of the intimal tear, (2) the positional relationship between the impact site and the entry tear, and (3) the circumstance of clash impact onto the "cushion" of accumulated waste in the refuse pit. Inquiries into the cause of death, such as those made in this report, are required to provide detailed information on the circumstances of the accident, postmortem examinations, and careful consideration.

Anterior Tricuspid Leaflet Cleft in an Adult Male: An Autopsy Case Report.

The deceased was a 44-year-old male who was treated for a suspected Ebstein's anomaly observed using transthoracic echocardiogram. He was found dead in his bed at home. Autopsy revealed that the septal tricuspid leaflet was intact; however, a large anterior tricuspid leaflet cleft and right atrioventricular cavity dilation were observed. Pathological examination revealed a normal tricuspid valve, except for the presence of a cleft with local fibrosis of the left ventricle papillary muscle and hemosiderin-containing macrophages at both lungs. There were no other abnormalities that may have led to death. It was concluded that he died a cardiac death based on the right heart overload associated with the anterior tricuspid leaflet cleft. This case indicates the possibility that the anterior tricuspid leaflet cleft can cause death and also highlights the necessity of a detailed autopsy to accurately diagnose the cause of death.

Wide distribution of alpha-synuclein oligomers in multiple system atrophy brain detected by proximity ligation.

Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disease that is characterized by varying degrees of cerebellar dysfunction and Parkinsonism. The neuropathological hallmark of MSA is alpha-synuclein (AS)-positive glial cytoplasmic inclusions (GCIs). Although severe neuronal loss (NL) is also observed in MSA, neuronal inclusions (NIs) are rare compared to GCIs, such that the pathological mechanism of NL in MSA is unclear. GCIs and NIs are late-stage pathology features relative to AS oligomers and may not represent early pathological changes in MSA. To reveal the early pathology of MSA, it is necessary to examine the early aggregation of AS, i.e., AS oligomers. Here, we adopted a proximity ligation assay (PLA) to examine the distribution of AS oligomers in brain tissue samples from patients with MSA and other diseases. Surprisingly, MSA brains showed a widespread distribution and abundant accumulation of oligomeric AS in neurons as well as oligodendrocytes of the neocortex. In several regions, oligomeric AS signal intensity was higher in cases with MSA than in cases with Parkinson's disease. In contrast to previous studies, AS-PLA revealed abundant AS oligomer accumulation in Purkinje cells in MSA brains, identifying oligomeric AS accumulation as a possible cause of Purkinje cell loss. This wide distribution of AS oligomers in MSA brain neurons has not been described previously and indicates a pathological mechanism of NL in MSA.

Rapid identification of Gloriosa superba and Colchicum autumnale by melting curve analysis: application to a suicide case involving massive ingestion of G. superba.

The plant species Gloriosa superba and Colchicum autumnale produce extremely poisonous colchicine as a major toxic metabolite. Almost all previous studies on colchicine poisoning have focused on drug analysis and clinical and pathological aspects. In this study, we developed a rapid, highly sensitive method to identify G. superba and C. autumnale. This method, which can distinguish between G. superba and C. autumnale using even minute amounts of plant material, is based on duplex real-time PCR in combination with melting curve analysis. To discriminate between the two genera of colchicine-containing plants, we designed new primer pairs targeting the region of the ycf15 gene, which is present in C. autumnale but not G. superba. By producing PCR amplicons with easily distinguishable melting temperatures, we were able to rapidly and accurately distinguish G. superba from C. autumnale. The new primer pairs generated no PCR amplicons from commercially available human DNA or various plant DNAs except for G. superba and C. autumnale. Sensitivity testing indicated that this assay can accurately detect less than 0.031 ng of DNA. Using our method in conjunction with colchicine drug analysis, we successfully identified G. superba in the stomach contents of a suicide victim who ingested massive quantities of a colchicine-containing plant. According to these results, duplex real-time PCR analysis is very appropriate for testing forensic samples, such as stomach contents harboring a variety of vegetables, and enables discrimination between G. superba and C. autumnale in forensic and emergency medical fields.

Autopsy Case of a Penetrating Wound to the Left Cerebral Hemisphere Caused by an Accidental Shooting With a Crossbow.

A crossbow is a bow that shoots an arrow when a gun-like trigger is pulled. Deaths caused by accidental crossbow shootings are extremely rare. Here we describe an autopsy case of a penetrating wound to the left cerebral hemisphere caused by an accidental shooting with a crossbow. A man in his early 60s who lived with his wife and had used crossbows for 20 years as his hobby was found one early morning in the shed of his house, collapsed and bleeding from the head and neck. He was taken to a hospital and died after approximately 3 days of conservative treatment. At autopsy, a penetrating wound between the upper part of the left anterior neck and the left frontoparietal region was evident. Traumatic intracerebral hematoma was observed in the left frontal lobe, and severe traumatic subarachnoid hemorrhage was present throughout the brain. Cerebral contusion and hematoma without any organization were noted around the penetration. The cause of death was determined to be cerebral contusion and intracerebral hematoma due to the penetrating wound by the crossbow arrow. He was probably trying to load an arrow into the crossbow by placing it on the floor, pointing upward, and made a mistake in its operation that resulted in the shooting of the arrow. This case is unique because it was a rare accidental death caused by a crossbow arrow, and a detailed histopathological examination was performed.

Postmortem interval estimation: a novel approach utilizing gas chromatography/mass spectrometry-based biochemical profiling.

While the molecular mechanisms underlying postmortem change have been exhaustively investigated, the establishment of an objective and reliable means for estimating postmortem interval (PMI) remains an elusive feat. In the present study, we exploit low molecular weight metabolites to estimate postmortem interval in mice. After sacrifice, serum and muscle samples were procured from C57BL/6J mice (n = 52) at seven predetermined postmortem intervals (0, 1, 3, 6, 12, 24, and 48 h). After extraction and isolation, low molecular weight metabolites were measured via gas chromatography/mass spectrometry (GC/MS) and examined via semi-quantification studies. Then, PMI prediction models were generated for each of the 175 and 163 metabolites identified in muscle and serum, respectively, using a non-linear least squares curve fitting program. A PMI estimation panel for muscle and serum was then erected which consisted of 17 (9.7%) and 14 (8.5%) of the best PMI biomarkers identified in muscle and serum profiles demonstrating statistically significant correlations between metabolite quantity and PMI. Using a single-blinded assessment, we carried out validation studies on the PMI estimation panels. Mean ± standard deviation for accuracy of muscle and serum PMI prediction panels was -0.27 ± 2.88 and -0.89 ± 2.31 h, respectively. Ultimately, these studies elucidate the utility of metabolomic profiling in PMI estimation and pave the path toward biochemical profiling studies involving human samples.

Fatal acute lemborexant Poisoning: An autopsy case report.

A 50-year-old male was found dead in a park. Postmortem analysis using liquid chromatography-tandem mass spectrometry revealed lemborexant concentrations of 1.651 µg/mL in blood from the right heart, 0.236 µg/mL in the urine, and 58.642 µg/mL in the stomach contents. Based on the autopsy findings and postmortem analyses, the cause of death was identified as acute lemborexant poisoning due to an overdose. Although lemborexant is generally considered safe, its excessive ingestion can be fatal. Since no lethal concentration of lemborexant has been reported, the blood levels in this case can serve as a reference. Despite its widespread clinical use, lemborexant is not detected by the rapid urine drug screening tests currently available in Japanese investigative agencies. Forensic pathologists must be vigilant in order not to overlook acute lemborexant poisoning.

Association study of a single nucleotide polymorphism in the hypoxia response element of the macrophage migration inhibitory factor gene promoter with suicide completers in the Japanese population.

BACKGROUND: More than 800 000 people die by suicide annually. The heritability of suicide is 30%-50%. We focused on the hypoxia response element (HRE), which promotes the expression of macrophage migration inhibitory factor (MIF) via the hypoxia-inducible factor (HIF) pathway, important in neurogenesis and neuroprotection. We examined a genetic polymorphism of rs17004038, a single-nucleotide polymorphism (SNP), in suicide completers and controls. METHODS: The study population included 1336 suicide completers and 814 unrelated healthy controls. All participants were Japanese. We obtained peripheral blood, extracted DNA, and genotyped the patients for SNP rs17004038 (C > A). RESULTS: No significant differences were observed between the two groups in either the allele or genotype analyses. Subgroup analyses by sex, age (<40 or ≥40), and suicide method (violent or nonviolent suicide) were performed with similar results. CONCLUSION: No association was observed between SNP rs17004038 and suicide completion. Although it is challenging to collect a large number of samples from suicide completers, further MIF-related genetic studies, including those of rs17004038, are necessary with larger sample sizes.

Estimates of exposure to cold before death from immunohistochemical expression patterns of HSP70 in glomerular podocytes.

Environmental factors such as outside temperature at the time of death are very important for forensic diagnoses and police investigations. In particular, death in a cold environment is associated with factors of forensic interest, including hypothermia, drowning in cold water, or postmortem body movement by a suspect. Hypothermia raises a special problem because of the difficulty of evaluation during autopsy. We describe here a unique method of estimating antemortem environmental temperature, involving the immunohistochemical analysis of HSP70 expression patterns in glomerular podocytes. Using this method, we found that HSP70 was present in glomerular podocytes at autopsy and that HSP70 was highly expressed, mainly in the nucleus of podocytes, in deaths associated with exposure to cold. Interestingly, this expression pattern was specific to death in a cold environment, including hypothermia and drowning in cold water. Analysis of the pattern of HSP70 expression in glomeruli may therefore be very useful in forensic diagnosis, for determining whether the antemortem environmental temperature was low. Moreover, immunohistochemical and real-time PCR assays of the molecular mechanism of HSP70 and HSF1 expression in glomeruli following exposure to cold indicated that HSP70 was rapidly translocated to the nucleus of podocytes following exposure to cold, but without new protein synthesis.

Ribosomal DNA gene copies are increased in blood and brain of Japanese schizophrenia patients.

Past evidence has indicated increased ribosomal DNA (rDNA) content in the blood of patients with schizophrenia (SCZ) among European populations. Here, for the first time, we investigated the rDNA copy number (rDNAcn) of SCZ in East Asian populations as well as in blood and brain tissues. In this study, we measured 18S/28S rDNAcn in the peripheral blood of live participants (81 patients with SCZ and 98 healthy controls) and the dorsolateral prefrontal cortices (DLPFCs) of postmortem individuals (10 patients with SCZ and 23 non-psychiatric controls) in the Japanese population. Patients with SCZ had significantly increased 18S/28S rDNAcn in the blood compared to controls (p < 0.05). 18S rDNAcn was significantly increased in the brain of patients with SCZ compared to controls (p < 0.05). In conclusion, regarding the increased rDNAcn in the blood of patients with SCZ that was previously reported in Europeans, we successfully replicated this by using a different, ethnically East Asian, cohort. Additionally, we provide the first evidence of increased rDNAcn in the brain of patients with SCZ. These findings may help to elucidate the molecular underpinnings of SCZ pathophysiology related to ribosomal DNA abnormalities.

Association of two variable number of tandem repeats in the monoamine oxidase A gene promoter with suicide completion: The present study and meta-analysis.

BACKGROUND: One potential cause of suicide is serotonergic dysfunction. Sex differences have been reported to modulate the effects of serotonergic polymorphisms. Monoamine oxidase A (MAOA) is an enzyme that degrades serotonin and is located on the X chromosome. A previous study indicated that the upstream (u) variable number of tandem repeat (VNTR) in the MAOA gene promoter may be associated with suicide. However, a meta-analysis showed that this polymorphism may not be related to suicide. According to a recent study, compared with the uVNTR, the distal (d)VNTR and the haplotypes of the two VNTRs modulate MAOA expression. METHODS: We examined the two VNTRs in the MAOA gene promoter in 1007 subjects who committed suicide and 844 healthy controls. We analyzed the two VNTRs using fluorescence-based polymerase chain reaction assays. We conducted a meta-analysis for the two VNTRs to update it. RESULTS: Our results demonstrated that neither the genotype-based associations nor allele/haplotype frequencies of the two VNTRs were significantly associated with suicide. In the meta-analysis, we did not indicate relationships between uVNTR and suicide nor did we identify articles analyzing dVNTR in suicide. CONCLUSION: Overall, we did not find a relationship between the two VNTRs in the MAOA promoter and suicide completion; thus, warranting further studies are required.

Role of afadin in vascular endothelial growth factor- and sphingosine 1-phosphate-induced angiogenesis.

RATIONALE: Angiogenesis contributes to physiological and pathological conditions, including atherosclerosis. The Rap1 small G protein regulates vascular integrity and angiogenesis. However, little is known about the effectors of Rap1 involved in angiogenesis. It is not known whether afadin, an adherens junction protein that connects immunoglobulin-like adhesion molecule nectins to the actin cytoskeleton and binds activated Rap1, plays a role in angiogenesis. OBJECTIVE: We investigated the role of endothelial afadin in angiogenesis and attempted to clarify the underlying molecular mechanism. METHODS AND RESULTS: Treatment of human umbilical vein endothelial cells (HUVECs) with vascular endothelial growth factor (VEGF) and sphingosine 1-phosphate (S1P) induced the activation of Rap1. Activated Rap1 regulated intracellular localization of afadin. Knockdown of Rap1 or afadin by small interfering RNA inhibited the VEGF- and S1P-induced capillary-like network formation, migration, and proliferation, and increased the serum deprivation-induced apoptosis of HUVECs. Knockdown of Rap1 or afadin decreased the accumulation of adherens and tight junction proteins to the cell-cell contact sites. Rap1 regulated the interaction between afadin and phosphatidylinositol 3-kinase (PI3K), recruitment of the afadin-PI3K complex to the leading edge, and the activation of Akt, indicating the involvement of Rap1 and afadin in the PI3K-Akt signaling pathway. Binding of afadin to Rap1 regulated the activity of Rap1 in a positive-feedback manner. In vivo, conditional deletion of afadin in mouse vascular endothelium using a Cre-loxP system impaired the VEGF- and S1P-induced angiogenesis. CONCLUSIONS: These results demonstrate a novel molecular mechanism by which Rap1 and afadin regulate the VEGF- and S1P-induced angiogenesis.

Effect of FURIN SNP rs17514846 on coronary atherosclerosis in human cardiac specimens: An autopsy study of 106 cases.

BACKGROUND: Coronary artery disease (CAD), including coronary atherosclerosis (CAS), is one of the most common causes of death. The FURIN SNP rs17514846 is assumed to be a risk factor for CAD. We evaluated this relationship using autopsy specimens and autopsy data, such as the histopathological degree of CAS. MATERIALS AND METHODS: A total of 106 samples were genotyped from obtained blood samples. Myocardial and coronary arterial FURIN levels were quantified by ELISA. The degree of CAS was classified histopathologically according to the Stary classification, and the localization of FURIN was examined by immunostaining. The obtained data were analyzed statistically. RESULTS: FURIN expression was widely observed in the myocardium, vascular smooth muscle cells, endothelial cells, adipocytes, and macrophages. FURIN level in the myocardium of cases with the AA genotype at the FURIN SNP rs17514846 was higher than that in CC cases. Additionally, FURIN levels in both coronary arteries and myocardium were higher at the early stage of CAS than at the late stage microscopically. CONCLUSION: Our study suggested that the A allele of rs17514846 is associated with higher FURIN level in the heart and that FURIN exhibits a higher level in the early stage of CAS. These findings deepen our understanding of the mechanism of CAS.

An autopsy case report of aortic dissection complicated with histiolymphocytic pericarditis and aortic inflammation after mRNA COVID-19 vaccination.

A male in his 90 s consulted a doctor because he experienced several days of general fatigue and dyspnea. He was diagnosed with heart failure, and diuretic medications taken for 3 days relieved his symptoms. However, he was found dead on the morning of the fourth day after consultation. He had received a third dose of coronavirus disease 2019 (COVID-19) vaccine approximately 2 weeks before death. An autopsy revealed dissection of the ascending aorta and pericardial hemotamponade. The heart showed a white villous surface, and the pericardium was fibrously thick. Microscopic examination revealed pericarditis with predominantly macrophage and lymphocyte infiltration. These histological findings were compatible with those of post-vaccination myocarditis. To the best of our knowledge, histopathologically proven pericarditis after COVID-19 vaccination has not been reported. In the present case, extended inflammation of the aortic adventitia was a possible cause of aortic wall fragility followed by dissection.

Immunohistochemical analysis of CD31 expression in myocardial tissues from autopsies of patients with ischemic heart disease.

CD31, a transmembrane protein expressed on endothelial and hematopoietic cells, plays important roles in leukocyte trafficking, mechanotransduction, angiogenesis, vascular permeability, and regulation of cellular responsiveness. CD31 immunoreactivity is employed as a sensitive and specific endothelial marker in diagnostic pathology. In this study, CD31 expression in myocardial tissues from deceased patients with ischemic heart disease and a mouse model of acute myocardial infarction were examined by immunohistochemical staining. We examined 24 neutral formalin-fixed, paraffin-embedded myocardial tissue samples obtained within 48 h postmortem from the autopsies of patients who were diagnosed with ischemic heart disease. CD31 expression was observed in vascular endothelial and endocardial cells. In necrotic myocardium, diffusion of CD31 antigen was observed. Elevated CD31 expression was observed around myocardial cells undergoing remodeling, suggesting that endothelial proliferation occurred at these sites. In contrast, fibrotic myocardial foci did not show upregulated CD31 expression. The same CD31 expression characteristics as those observed in the human samples were observed in the mouse model. CD31 immunostaining as an endothelial and microvasculature marker may be a useful complement to conventional staining techniques currently used in the diagnosis of ischemic heart disease, and may allow the timing and process of myocardial remodeling to be analyzed in detail.

Immunohistochemical analysis of vimentin expression in myocardial tissue from autopsy cases of ischemic heart disease.

Vimentin is a type III intermediate filament cytoskeletal protein that is expressed mainly in cells of mesenchymal origin and is involved in a plethora of cellular functions. In this study, myocardial tissues from patients with ischemic heart disease and a mouse model of acute myocardial infarction were subjected to immunohistochemistry for vimentin. We first examined 26 neutral formalin-fixed, paraffin-embedded myocardial tissue samples from autopsies of patients that were diagnosed with ischemic heart disease within 48 h postmortem. Myocardial cells were negative for vimentin, whereas non-myocardial cells, including vascular endothelium, vascular smooth muscle, fibroblasts, nerve fibers, adipocytes and mesothelial cells, showed positivity. Elevated vimentin expression was observed around myocardial cells undergoing remodeling, suggesting fibroblastic and endothelial proliferation in these locations. By contrast, myocardial foci that were completely fibrotic did not show upregulated vimentin expression. Inflammatory foci including macrophages and neutrophils were clearly visualized with vimentin immunostaining. The same vimentin expression phenomena as those found in human samples were observed in the mouse model. Our study indicates that immunostaining of vimentin as a marker for myocardial remodeling and the dynamics of all non-myocardial cell types may be useful for supplementing conventional staining techniques currently used in the diagnosis of ischemic heart disease.

Quantitative analysis of thiamylal and its metabolite secobarbital using liquid chromatography-tandem mass spectrometry in adipose tissue, serum, and liver.

Thiamylal is an ultrashort-acting barbiturate used for intravenous administration or general anesthesia induction. However, some cases of poisoning and suicide with thiamylal administration have been reported. Additionally, there are few reports on its analysis in the organs and adipose tissue, which requires purification by column chromatography and evaporation. A rapid and sensitive method was developed for quantifying thiamylal and its metabolite, secobarbital, in the adipose tissue, serum, and liver using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Samples were prepared using modified QuEChERS extraction. For adipose tissue samples, an acetonitrile-hexane partitioning step was added to the extraction. This method was applied to investigate a suspected self-poisoning autopsy case. The quantitation accuracy for thiamylal added to porcine pericardial fat (0.18 µg/g), human serum (0.015 µg/mL), and porcine liver (0.18 µg/g) was 103%, 113%, and 95.3%, respectively. The quantitation limits calculated for porcine pericardial fat, human serum, and porcine liver at a signal-to-noise ratio of 10 were 0.06 µg/g, 0.005 µg/mL, and 0.06 µg/g, respectively. In addition, the thiamylal and secobarbital levels in the forensic autopsy case were 140 and 1.5 µg/g, respectively, in myocardial fat; 3.5-4.9 and 0.12-0.20 µg/mL, respectively, in serum; and 6.2-42 and 0.58-1.1 µg/g, respectively, in liver tissue. Thiamylal is especially distributed in the adipose tissue. The thiamylal-to-fat ratio may help estimate the time from administration to death. The developed modified QuEChERS extraction method with acetonitrile-hexane partitioning is suitable for analyzing hydrophobic compounds, such as thiamylal, in the adipose tissue.

Immunohistochemical analysis of von Willebrand factor expression in myocardial tissues from autopsies of patients with ischemic heart disease.

von Willebrand factor (VWF) plays a crucial role in hemostasis and thrombosis. VWF is involved in platelet attachment to the subendothelium, serving as a carrier protein for coagulation factor VIII. In this study, myocardial tissues from deceased patients with ischemic heart disease and a mouse model of acute myocardial infarction were subjected to immunohistochemistry to determine VWF expression. We examined 28 neutral formalin-fixed, paraffin-embedded myocardial tissue samples obtained from the autopsies of patients who were diagnosed with ischemic heart disease within 48 h postmortem. Most myocardial cells were negative for VWF, although some cells showed nonspecific positivity. Elevated VWF expression was observed around myocardial cells undergoing remodeling, suggesting that endothelial proliferation occurred at these sites. In contrast, completely fibrotic myocardial foci did not show upregulated VWF expression. Positivity in fibrin deposition and hemorrhagic sites was observed. The same VWF expression characteristics as those observed in the human samples were observed in the mouse model. VWF immunostaining as an endothelial marker may be a useful supplementation to conventional staining techniques that are currently used in the diagnosis of ischemic heart disease in terms of examining the timing of myocardial remodeling in detail and highlighting the remodeling process.