順天堂大学医学部内科学教室循環器内科学講座※Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine― 72 ―The Aim of this study was to 1) Establish the concept and biomarker of Age-related Fibrotic Disorder (A-FiD), 2) Generate therapies for A-FiD. Here I define A-FiD as disorders including heart failure with preserved ejection fraction (HFpEF), atrial fibrillation (Afib), chronic kidney disease (CKD), sarcopenia or metabolic dysfunction associated steatotic liver disease (MASH) etc. Recently, I identified a circulating Age-related pro-Fibrotic Protein (AFP) in plasma of 1) aged individuals, 2) HFpEF, 3) Afib or 4) MASH patients. Dietary obesity increased AFP in plasma, and pilot studies analyzing loss or gain of function models showed AFP becomes pathogenic in HFpEF, atrial fibrillation, sarcopenia or MASH models. Comprehensive studies including transgenic mice showed AFP has causal roles for the progression of pathogenesis in MASH. Our ongoing studies also indicate this molecule would become draggable target for HFpEF.※国立循環器病研究センター心血管老化制御部※Department of Cardiovascular Aging, National Cerebral and Cardiovascular CenterAbstractはじめに本研究課題で，加齢関連線維性疾患（Age-related Fibrotic Disorders (A-FiD)）の疾患概念の確立，２）A-FiDに対する臓器・疾患横断的治療法の開発，に挑んだ．A-FiDは拡張不全型心不全(HFpEF)，心房細動，慢性腎障害(CKD)，非アルコール性脂肪性肝炎(MASH)など，加齢と共に罹患率が増加し組織の線維化が中心的病態を形成する疾患，と新しく定義した．本研究の目的は，A-FiDに対する疾患横断的な治療法を開発することであり，AFPを標的とした治療法の開発を目指した．特にMASHとHFpEFの病態に着目し，AFP抑制による新規治療法の開発に挑戦した．加齢とともに血液中のAFPのレベルが有意に増加するため，AFPを「老化促進タン「加齢関連線維性疾患」病態概念の確立及び治療法開発Developing…next…generation…therapy…for…Age-related…Fibrotic…Disorders…targeting…secreted…type…pro-fibrotic…protein清水 逸平Ippei Shimizu
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