Department of Cardiovascular Medicine, The University of Tokyo HospitalAbstract東京大学医学部附属病院循環器内科― 67 ―The prognosis of heart failure remains poor, and there is a demand for the development of innovative treatment strategies for heart failure. Recently, an increase in the incidence of heart failure has been reported to be associated with the hypertrophy of pericardial adipose tissue (PAT). Although intervention targeting PAT may provide a completely new therapeutic target for heart failure, the specific molecular mechanisms remain unclear. This study aimed to elucidate the tissue relationship between PAT and heart failure.Firstly, to investigate the impact of PAT hypertrophy on heart failure, we created a cardiac pressure overload stress model using transverse aortic constriction (TAC) and inducing PAT hypertrophy by a high-fat diet (HFD)-feeding. Four weeks after TAC, significant deterioration of cardiac function was observed in the group with hypertrophic PAT, whereas cardiac function was maintained in the HFD-fed group where PAT was removed at the time of TAC surgery. Consistent with clinical studies, this result demonstrated in a mouse model that PAT hypertrophy exacerbates heart failure. Hypertrophic PAT exhibited increased accumulation of immune cells and inflammatory cytokines compared to normal PAT, along with increased fibrotic area in the heart after TAC. These results suggest that hypertrophic PAT may act on the myocardium through secreting certain factors. Therefore, we are currently conducting single-cell transcriptome analysis of PAT to identify specific cell types and secretory factors that are characteristic of enlarged PAT.Furthermore, we observed a phenomenon of fat “beiging” in hypertrophic PAT. To investigate the significance of local fat beiging in PAT, we attempted to create genetically modified mice expressing Cre restricted to the light-exposed area. Using a photoactivatable Cre-loxP system (PA-Cre), we crossed PA-Cre mice with R26-tdTomato reporter mice and confirmed expression of the reporter gene locally in the pericardial 心臓周囲脂肪と心臓の組織間ネットワークの解明とIntra-organ…network…of…pericardial…fat…and…the…heart新規心不全治療法の開発基盤構築in…the…development…of…heart…failure上田 和孝Kazutaka Ueda
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