摘要
Cardiac fibrosis is defined as the unbalanced production and degradation of cardiac interstitial extracellular matrix(ECM),leading to systolic and diastolic dysfunction,arrhythmias,and adverse outcomes of many cardiac pathophysiological conditions.The accumulation of myocardial ECM increases the risk of arrhythmias and impairs cardiac function,ultimately leading to the development of heart failure.Although slowing or reversing the development of excessive accumulation of ECM and cardiac fibrosis is important for maintaining cardiac function,there is currently no approved treatment for them.Activated cardiac fibroblasts are the main effector cells of cardiac fibrosis.Their expansion after pathophysiologic stimuli such as pressure overload,volume overload,metabolic dysfunction,wound healing,and aging is primarily driven by activating resident interstitial populations.While cardiac fibroblasts are the primary effector cells in the fibrotic heart,monocytes/macrophages,lymphocytes,mast cells,vascular cells,and cardiomyocytes may also contribute to the fibrotic response,by secreting critical fibrotic factors and matricellular proteins.This review discusses histological features,molecular pathways involved in the pathogenesis of cardiac fibrosis and possible therapeutic targets.Understanding the occurrence,development and diffusion mechanisms of cardiac fibrosis has important clinical implications for the discovery of drugs to prevent the progression of cardiac fibrosis.
作者
SUN Jian-jian
ZHONG Tao
ZHU Ping
孙建建;钟涛;朱平(Department of Cardiac Surgery,and Department of Medical Research Center,Guangdong Cardiovascular Institute,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangdong Provincial Key Laboratory of Pathogenesis,Targeted Prevention and Treatment of Heart Disease,Guangzhou,Guangdong 510080,China;Shanghai Key Laboratory of Regulatory Biology,Institute of Molecular Medicine,East China Normal University,School of Life Sciences,200241,Shanghai,P.R.China)
基金
supported by National Key Research and Development Program of China(NO.2018YFA0108700,NO.2017YFA0105602)
NSFC Projects of International Cooperation and Exchanges(NO.81720108004)
National Natural Science Foundation of China(NO.82100275,81974019)
The Research Team Project of Natural Science Foundation of Guangdong Province of China(NO.2017A030312007)
The key program of guangzhou science research plan(201904020047)
The Special Project of Dengfeng Program of Guangdong Provincial People’s Hospital(NO.DFJH201812
NO.KJ012019119,NO.KJ012019423)
