The University of Tokyo · 의학
Toshiyuki Ko 교수의 연구실은 심장질환의 핵심 기전인 섬유화와 DNA 손상, 핵 구조 이상에 초점을 맞춘 기초-임상 연계 연구를 수행하고 있습니다. 특히 심장섬유아세포의 활성화를 조절하는 HTRA3 단백질, DNA 손상 반응, 라미나 기능 이상이 초래하는 심장기능 저하 등 심장질환의 분자 기전을 단일세포 유전자발현, 공간 전사체 분석, 유전자 편집 기법을 통해 규명하고 있습니다. 이는 심부전 예방 및 개인 맞춤형 치료 전략 개발에 기여할 잠재력을 지닌 연구입니다.
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Tissue fibrosis and organ dysfunction are hallmarks of age-related diseases including heart failure, but it remains elusive whether there is a common pathway to induce both events. Through single-cell RNA-seq, spatial transcriptomics, and genetic perturbation, we elucidate that high-temperature requirement A serine peptidase 3 (Htra3) is a critical regulator of cardiac fibrosis and heart failure by maintaining the identity of quiescent cardiac fibroblasts through degrading transforming growth fa
This study evaluated myocardial nuclear staining for the DNA damage markers poly(ADP-ribose) (PAR) and γ-H2A.X in 58 patients with dilated cardiomyopathy. Patients with left ventricular reverse remodeling (LVRR) showed a significantly smaller proportion of PAR-positive nuclei and γ-H2A.X-positive nuclei in biopsy specimens compared with those without LVRR. Propensity analysis showed that the proportion of both PAR-positive and γ-H2A.X-positive nuclei were independent prognostic factors for LVRR.
Mutations in the <i>LMNA</i> gene encoding Lamin A and C (Lamin A/C), major components of the nuclear lamina, cause laminopathies including dilated cardiomyopathy (DCM), but the underlying molecular mechanisms have not been fully elucidated. Here, by leveraging single-cell RNA sequencing (RNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), protein array, and electron microscopy analysis, we show that insufficient structural maturation of cardiomyocytes owing to trap
In patients with PAD, OS was largely defined by comorbidities but not by lesion location. The background risk factors, underlying comorbidities, and event rates were different according to PAD location, suggesting that stratified treatment should be established for different patient populations.
Pathological heart injuries such as myocardial infarction induce adverse ventricular remodeling and progression to heart failure owing to widespread cardiomyocyte death. The adult mammalian heart is terminally differentiated unlike those of lower vertebrates. Therefore, the proliferative capacity of adult cardiomyocytes is limited and insufficient to restore an injured heart. Although current therapeutic approaches can delay progressive remodeling and heart failure, difficulties with the direct
Our analysis using a large-scale epidemiological dataset presented the dose-dependent association between eGFR decline and the risk of depression, which highlights the importance of incorporating mental health assessments into the routine care of patients with kidney dysfunction, regardless of the stage of their disease.
in which the cause of death is clarified by postmortem genetic testing is very important and has been already mentioned international guidelines or statements. n this issue of the Journal, Hata al report a study of postmortem genetic testing with whole-exome sequencing for 10 autopsy cases of idiopathic bradyarrhythmia. 5 Although genetic investigation of idiopathic bradyarrhythmia has been limited so far, their study clearly demonstrated evidence that genetic factors considerably contribute to
Despite the lower prevalence of SAS among women, there was a gender disparity in the cardiovascular impact of SAS, with women demonstrating a significantly higher risk compared with men. This underscores the importance of tailored management strategies aimed at early detection and CVD prevention specifically in female patients with SAS.
Journal Article Accepted manuscript Applying the HARMS2-AF Risk Score for Japanese population: An analysis of a nationwide epidemiological dataset Get access Toshiyuki Ko, MD, PhD, Toshiyuki Ko, MD, PhD Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar Yuta Suzuki, PhD, Yuta Suzuki, PhD Department of Cardiovascular Medicine, Graduate School of Medicine, The University