Alex M. Parker MBiomedSc , Jarmon G. Lees PhD , Andrew J. Murray PhD , Anida Velagic PhD , Shiang Y. Lim MPharm, PhD , Miles J. De Blasio PhD , Rebecca H. Ritchie PhD
{"title":"精密医学","authors":"Alex M. Parker MBiomedSc , Jarmon G. Lees PhD , Andrew J. Murray PhD , Anida Velagic PhD , Shiang Y. Lim MPharm, PhD , Miles J. De Blasio PhD , Rebecca H. Ritchie PhD","doi":"10.1016/j.jacbts.2025.101345","DOIUrl":null,"url":null,"abstract":"<div><div>A substantial component of the increasing global burden of cardiovascular disease is attributed to heart failure (HF), affecting over 64 million adults worldwide. Maladaptive mitochondrial respiratory alterations and oxidative stress are major contributors to HF development and progression, with subsequent downstream myocardial energetic impairment as a strong predictor of mortality. Current conventional therapeutic approaches, including renin-angiotensin-aldosterone system inhibition and β-adrenergic blockade, target neurohormonal aspects of HF and are effective in slowing disease progression. However, although these therapies may be associated with some improvement in myocardial energetics, they do not specifically address alterations in myocardial mitochondrial respiration or redox homeostasis. Targeting mitochondria has hence become a promising approach for more effective and tailored therapies. This review summarizes metabolic derangements that drive HF progression, with a specific focus on mitochondria. Importantly, here we address the essential knowledge gaps in the field, highlighting key translational strategies used to date, and the challenges associated with therapeutically targeting mitochondrial pathways, alongside recent developments seeking to deploy novel mitochondrial-targeted therapeutic approaches to treat HF.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101345"},"PeriodicalIF":8.4000,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Precision Medicine\",\"authors\":\"Alex M. Parker MBiomedSc , Jarmon G. Lees PhD , Andrew J. Murray PhD , Anida Velagic PhD , Shiang Y. Lim MPharm, PhD , Miles J. De Blasio PhD , Rebecca H. Ritchie PhD\",\"doi\":\"10.1016/j.jacbts.2025.101345\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>A substantial component of the increasing global burden of cardiovascular disease is attributed to heart failure (HF), affecting over 64 million adults worldwide. Maladaptive mitochondrial respiratory alterations and oxidative stress are major contributors to HF development and progression, with subsequent downstream myocardial energetic impairment as a strong predictor of mortality. Current conventional therapeutic approaches, including renin-angiotensin-aldosterone system inhibition and β-adrenergic blockade, target neurohormonal aspects of HF and are effective in slowing disease progression. However, although these therapies may be associated with some improvement in myocardial energetics, they do not specifically address alterations in myocardial mitochondrial respiration or redox homeostasis. Targeting mitochondria has hence become a promising approach for more effective and tailored therapies. This review summarizes metabolic derangements that drive HF progression, with a specific focus on mitochondria. Importantly, here we address the essential knowledge gaps in the field, highlighting key translational strategies used to date, and the challenges associated with therapeutically targeting mitochondrial pathways, alongside recent developments seeking to deploy novel mitochondrial-targeted therapeutic approaches to treat HF.</div></div>\",\"PeriodicalId\":14831,\"journal\":{\"name\":\"JACC: Basic to Translational Science\",\"volume\":\"10 9\",\"pages\":\"Article 101345\"},\"PeriodicalIF\":8.4000,\"publicationDate\":\"2025-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JACC: Basic to Translational Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2452302X25002979\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACC: Basic to Translational Science","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452302X25002979","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
A substantial component of the increasing global burden of cardiovascular disease is attributed to heart failure (HF), affecting over 64 million adults worldwide. Maladaptive mitochondrial respiratory alterations and oxidative stress are major contributors to HF development and progression, with subsequent downstream myocardial energetic impairment as a strong predictor of mortality. Current conventional therapeutic approaches, including renin-angiotensin-aldosterone system inhibition and β-adrenergic blockade, target neurohormonal aspects of HF and are effective in slowing disease progression. However, although these therapies may be associated with some improvement in myocardial energetics, they do not specifically address alterations in myocardial mitochondrial respiration or redox homeostasis. Targeting mitochondria has hence become a promising approach for more effective and tailored therapies. This review summarizes metabolic derangements that drive HF progression, with a specific focus on mitochondria. Importantly, here we address the essential knowledge gaps in the field, highlighting key translational strategies used to date, and the challenges associated with therapeutically targeting mitochondrial pathways, alongside recent developments seeking to deploy novel mitochondrial-targeted therapeutic approaches to treat HF.
期刊介绍:
JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.