{"title":"亨廷顿氏病诱发的心脏疾病影响多种细胞通路","authors":"Girish C Melkani","doi":"10.20455/ros.2016.859","DOIUrl":null,"url":null,"abstract":"<p><p>Huntington's disease (HD) is a rare, inherited, progressive, and fatal neurological disorder resulting from expanded polyglutamine repeats in the huntingtin protein. While HD is predominately characterized as a disease of the central nervous system, mortality surveys and epidemiological studies reveal heart disease as one of the leading causes of death in HD patients. Emerging evidence supports a link between HD and cardiovascular disease, such as cardiac amyloidosis (accumulation of aggregates in the heart). Experimental animal and clinical studies have attempted to explain the mechanisms of HD-induced cardiac pathology in the association of protein misfolding, autophagic defects, oxidative stress, mitochondrial dysfunction, and cell death. HD is increasingly understood as a complex disease with peripheral components of cardiac and skeletal muscle pathophysiology. While the discovery of these linkages and apparent pathological markers is promising, the mechanism of HD-induced cardiac pathology and the nature of its cell autonomy remain elusive. Further study of the wide-ranging cardiac function in HD patients is needed. This review highlights published literature on the pathological factors associated with HD-induced cardiac amyloidosis and other cardiovascular diseases, and addresses gaps in this expanding area of study. Through comprehensive experimental and clinical studies, potential drugs can be tested to attenuate and/or ameliorate HD-induced cardiac pathology and mortality.</p>","PeriodicalId":91793,"journal":{"name":"Reactive oxygen species (Apex, N.C.)","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022757/pdf/nihms966717.pdf","citationCount":"0","resultStr":"{\"title\":\"Huntington's Disease-Induced Cardiac Disorders Affect Multiple Cellular Pathways.\",\"authors\":\"Girish C Melkani\",\"doi\":\"10.20455/ros.2016.859\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Huntington's disease (HD) is a rare, inherited, progressive, and fatal neurological disorder resulting from expanded polyglutamine repeats in the huntingtin protein. While HD is predominately characterized as a disease of the central nervous system, mortality surveys and epidemiological studies reveal heart disease as one of the leading causes of death in HD patients. Emerging evidence supports a link between HD and cardiovascular disease, such as cardiac amyloidosis (accumulation of aggregates in the heart). Experimental animal and clinical studies have attempted to explain the mechanisms of HD-induced cardiac pathology in the association of protein misfolding, autophagic defects, oxidative stress, mitochondrial dysfunction, and cell death. HD is increasingly understood as a complex disease with peripheral components of cardiac and skeletal muscle pathophysiology. While the discovery of these linkages and apparent pathological markers is promising, the mechanism of HD-induced cardiac pathology and the nature of its cell autonomy remain elusive. Further study of the wide-ranging cardiac function in HD patients is needed. This review highlights published literature on the pathological factors associated with HD-induced cardiac amyloidosis and other cardiovascular diseases, and addresses gaps in this expanding area of study. Through comprehensive experimental and clinical studies, potential drugs can be tested to attenuate and/or ameliorate HD-induced cardiac pathology and mortality.</p>\",\"PeriodicalId\":91793,\"journal\":{\"name\":\"Reactive oxygen species (Apex, N.C.)\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2016-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022757/pdf/nihms966717.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reactive oxygen species (Apex, N.C.)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.20455/ros.2016.859\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reactive oxygen species (Apex, N.C.)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.20455/ros.2016.859","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
亨廷顿氏病(Huntington's disease,HD)是一种罕见的遗传性、进行性和致命性神经系统疾病,由亨廷丁蛋白中的多聚谷氨酰胺重复序列扩增引起。虽然 HD 的主要特征是中枢神经系统疾病,但死亡率调查和流行病学研究显示,心脏病是导致 HD 患者死亡的主要原因之一。新的证据表明,HD 与心血管疾病(如心脏淀粉样变性(聚集在心脏中))之间存在联系。实验动物和临床研究试图从蛋白质错误折叠、自噬缺陷、氧化应激、线粒体功能障碍和细胞死亡等方面解释 HD 诱发心脏病变的机制。人们越来越认识到,HD 是一种复杂的疾病,具有心脏和骨骼肌病理生理学的外围成分。虽然发现这些联系和明显的病理标志物很有希望,但 HD 引发心脏病理变化的机制及其细胞自主性的性质仍然难以捉摸。需要对 HD 患者广泛的心脏功能进行进一步研究。本综述重点介绍了已发表的与 HD 诱导的心脏淀粉样变性和其他心血管疾病相关的病理因素的文献,并探讨了这一不断扩大的研究领域中存在的差距。通过全面的实验和临床研究,可以对潜在的药物进行测试,以减轻和/或改善 HD 引起的心脏病理变化和死亡率。
Huntington's disease (HD) is a rare, inherited, progressive, and fatal neurological disorder resulting from expanded polyglutamine repeats in the huntingtin protein. While HD is predominately characterized as a disease of the central nervous system, mortality surveys and epidemiological studies reveal heart disease as one of the leading causes of death in HD patients. Emerging evidence supports a link between HD and cardiovascular disease, such as cardiac amyloidosis (accumulation of aggregates in the heart). Experimental animal and clinical studies have attempted to explain the mechanisms of HD-induced cardiac pathology in the association of protein misfolding, autophagic defects, oxidative stress, mitochondrial dysfunction, and cell death. HD is increasingly understood as a complex disease with peripheral components of cardiac and skeletal muscle pathophysiology. While the discovery of these linkages and apparent pathological markers is promising, the mechanism of HD-induced cardiac pathology and the nature of its cell autonomy remain elusive. Further study of the wide-ranging cardiac function in HD patients is needed. This review highlights published literature on the pathological factors associated with HD-induced cardiac amyloidosis and other cardiovascular diseases, and addresses gaps in this expanding area of study. Through comprehensive experimental and clinical studies, potential drugs can be tested to attenuate and/or ameliorate HD-induced cardiac pathology and mortality.