Review
Biochemistry & Molecular Biology
Alexandrine Bertaud, Ahmad Joshkon, Xavier Heim, Richard Bachelier, Nathalie Bardin, Aurelie S. Leroyer, Marcel Blot-Chabaud
Summary: Cardiac fibrosis is a condition characterized by irreversible necrosis of the heart muscle, caused by various acute or chronic diseases, genetic alterations, or aging. Currently, there is no curative treatment available to prevent or attenuate cardiac fibrosis, which leads to progressive cardiac dysfunction and life-threatening outcomes. This review summarizes different targets and new strategies proposed to fight cardiac fibrosis, as well as discussing future directions, such as the use of exosomes or nanoparticles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Zhi-Teng Chen, Qing-Yuan Gao, Mao-Xiong Wu, Meng Wang, Run-Lu Sun, Yuan Jiang, Qi Guo, Da-Chuan Guo, Chi-Yu Liu, Si-Xu Chen, Xiao Liu, Jing-Feng Wang, Hai-Feng Zhang, Yang-Xin Chen
Summary: The study demonstrated the significant role of glycolysis in cardiac fibrosis post-myocardial infarction, with glycolysis inhibition showing potential in reducing cardiac fibroblast activation and fibrosis.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Review
Cardiac & Cardiovascular Systems
Ruoshui Li, Nikolaos G. Frangogiannis
Summary: Integrins, a family of surface receptors, play a role in sensing mechanical stress and changes in the matrix environment, and are involved in the regulation of fibrosis. In myocardial fibrosis, integrins are implicated in fibrogenic conversion of cardiac fibroblasts and may mediate recruitment and activation of fibrogenic macrophages. The role of integrins in cardiac fibrosis is dependent on the underlying pathologic condition and further research is needed to fully understand their involvement.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Review
Cell Biology
Julia Hohn, Wenbin Tan, Amanda Carver, Hayden Barrett, Wayne Carver
Summary: Changes in the extracellular matrix play a key role in tissue repair processes, especially during fibrosis where excessive matrix alters tissue function. Fibrosis was once thought to be progressive and irreversible, but recent studies have shown it can be stopped and even reversed. Therapeutic approaches targeting fibrosis and matrix-producing cells are being pursued more actively now.
Article
Multidisciplinary Sciences
Jian Huang, Luxin Wang, Yunli Shen, Shengqi Zhang, Yaqun Zhou, Jimin Du, Xiue Ma, Yi Liu, Dandan Liang, Dan Shi, Honghui Ma, Li Li, Qi Zhang, Yi-Han Chen
Summary: The kinase CLK4 regulates cardiac function by phosphorylating NEXN, and its deficiency may lead to pathological cardiac hypertrophy. CLK4 is a potential intervention target for the prevention and treatment of heart failure.
NATURE COMMUNICATIONS
(2022)
Review
Pharmacology & Pharmacy
Abhipree Sharma, Miles De Blasio, Rebecca Ritchie
Summary: Cardiomyopathy is a significant cardiac complication of diabetes, independent of other heart diseases. Pathological cardiac fibrosis, capillary rarefaction, and myocardial apoptosis contribute to its development. There are sex differences in the occurrence and treatment effects of diabetes, heart failure, and myocardial fibrosis.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Health Care Sciences & Services
Richard J. Roberts, Logan Hallee, Chi Keung Lam
Summary: Hsp90 is a key molecular chaperone that interacts with numerous disease pathways in cells, making it a potential therapeutic target. While small-molecule inhibition of Hsp90 activity may have cardiac toxicity, targeting Hsp90 through modulation of post-translational modifications (PTMs) could be a more attractive therapeutic strategy.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Multidisciplinary Sciences
Akito Eguchi, Ryan Coleman, Kenneth Gresham, Erhe Gao, Jessica Ibetti, J. Kurt Chuprun, Walter J. Koch
Summary: Pathological remodeling of the heart in chronic heart failure is linked to structural changes perpetuated by cardiac fibroblasts, with GRK5 playing a key role in regulating fibroblast activation and cardiac fibrosis. GRK5 inhibition shows potential beneficial effects in cardiac disease by preventing fibroblast activation and reducing fibrosis and hypertrophy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Prachi Umbarkar, Anand P. Singh, Sultan Tousif, Qinkun Zhang, Palaniappan Sethu, Hind Lal
Summary: Nintedanib (NTB) is an FDA-approved tyrosine kinase inhibitor for pulmonary fibrosis, and study shows its potential in reducing cardiac fibrosis and improving cardiac function in a murine heart failure model, suggesting its promising application in treating HF patients.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Ying Xie, Jing Yang, Kun Li, Fang Liu, Yi Yi, Ping Zhang
Summary: This case report describes a 52-year-old housewife diagnosed with hypocalcemic cardiomyopathy who presented with acute decompensated heart failure and hypocalcemia symptoms with a history of thyroidectomy. After diuresis and prompt electrolyte correction, shortness of breath and edema were relieved. However, there was evidence of non-reversible cardiac fibrosis after 1-year follow-up.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Cell Biology
Michael P. Czubryt, Taben M. Hale
Summary: Cardiac fibrosis is a characteristic of end-stage heart disease, but there are no approved therapies directly targeting the extracellular matrix. Research on cardiac fibroblasts is hindered by the lack of a clear marker.
CELLULAR SIGNALLING
(2021)
Article
Veterinary Sciences
Ga-Won Lee, Min-Hee Kang, Woong-Bin Ro, Doo-Won Song, Hee-Myung Park
Summary: The study found that dogs with heart, endocrine, and dermatologic diseases had higher circulatory galectin-3 levels compared to healthy dogs, with dogs with concentric cardiomyopathy showing significantly increased levels. Additionally, the conventional echocardiographic index E'/A' was positively associated with galectin-3 levels, and galectin-3 concentration could help evaluate cardiac remodeling and diastolic function in dogs. Further large-scale research is needed to understand the role of circulating galectin-3 in dogs with heart diseases.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Manabu Shiraishi, Ken Suzuki, Atsushi Yamaguchi
Summary: Excess deposition of extracellular matrix in the myocardium is associated with reduced left ventricular function. The mechanisms underlying the reversal of fibrosis are not well understood. This study investigated the role of myocardial tissue elasticity in influencing fibroblast phenotype. In vitro experiments using different culture conditions showed that fibroblasts differentiated into activated or matrix-degrading types based on the pericellular environment. Gene expression analysis identified Selenbp1 as a key regulator of fibroblast differentiation. Knockdown of Selenbp1 enhanced fibroblast activation and inhibited matrix degradation. In vivo knockdown of Selenbp1 resulted in tissue fibrosis and diastolic failure in the left ventricle. Selenbp1 appears to be a major molecule involved in regulating collagen turnover in cardiac fibrosis.
Article
Medicine, Research & Experimental
Giselle C. Melendez, Kylie Kavanagh, Nazli Gharraee, Jessica L. Lacy, Kevin H. Goslen, Masha Block, Jordyn Whitfield, Alexander Widiapradja, Scott P. Levick
Summary: The study showed that replacement substance P can reverse cardiac fibrosis in type 2 diabetes, independent of glycemic control. When used to treat diabetic monkeys, it was found that cardiac fibrosis decreased, left ventricular function improved, and no toxicities were observed.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Yan Wang, Miao Wang, Chrishan S. Samuel, Robert E. Widdop
Summary: Cardiac fibrosis, characterized by increased ECM deposition, is a hallmark of most cardiovascular diseases and inhibition of fibrosis could improve outcomes in heart failure patients. However, pharmacological treatment targeting ECM buildup remains limited. Animal models are important for understanding fibrosis pathogenesis and identifying new therapeutic targets.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)