Cardiac fibrosis in the ageing heart: Contributors and mechanisms.
Cardiac fibrosis refers to an excessive deposition of extracellular matrix (ECM) in cardiac tissue. Fibrotic tissue is stiffer and less compliant, resulting in subsequent cardiac dysfunction and heart failure. Cardiac fibrosis in the ageing heart may involve activation of fibrogenic signalling and inhibition of anti-fibrotic signalling, leading to an imbalance of ECM turnover. Excessive accumulation of ECM such as collagen in older patients contributes to progressive ventricular dysfunction. Overexpression of collagen is derived from various sources, including higher levels of fibrogenic growth factors, proliferation of fibroblasts and cellular transdifferentiation. These may be triggered by factors, such as oxidative stress, inflammation, hypertension, cellular senescence and cell death, contributing to age-related fibrotic cardiac remodelling. In this review, we will discuss the fibrogenic contributors in age-related cardiac fibrosis, and the potential mechanisms by which fibrogenic processes can be interrupted for therapeutic intent.
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.|School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Lu
L
Lu
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.|Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Jingbin
J
Guo
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.|School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Yue
Y
Hua
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.
Kevin
K
Huang
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.
Ruth
R
Magaye
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.
Jake
J
Cornell
Department of Medicine, St Vincent's Hospital, University of Melbourne, Melbourne, Vic., Australia.
Darren J
DJ
Kelly
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.|NHMRC Cardiovascular Centre of Research Excellence, School of Public Health, Curtin University, Perth, WA, Australia.
Christopher
C
Reid
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.
Danny
D
Liew
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Yingchun
Y
Zhou
Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Aihua
A
Chen
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.
Wei
W
Xiao
Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Qiang
Q
Fu
Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.
Bing Hui
0000-0001-9580-2548
BH
Wang
D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001343:Autophagy; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016922:Cellular Senescence; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D015398:Signal Transduction; D020257:Ventricular Remodeling
ageing; cardiac fibrosis; extracellular matrix turnover; fibrogenic factors; heart failure