Cardiac fibroblasts are a major cell population of the heart and are characterized by their capacity to produce extracellular matrix (ECM). In hearts subjected to pressure overload, excessive fibroblast accumulation is responsible for fibrosis of the myocardium, a major clinical issue. Hence, understanding mechanisms generating fibroblasts in this context has become a key question in the cardiovascular field. Recent studies now point to the activation of resident fibroblasts as the underlying cause of fibrosis. However, de novo generation of fibroblasts from endothelium and circulating hematopoietic cells has also been proposed to significantly contribute to fibrosis. Here, we discuss the latest findings on fibroblast origins, with a particular emphasis on the pressure overload model, and the implication of these findings for the development of anti-fibrotic therapies that are currently lacking.
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http://dx.doi.org/10.1007/s00109-015-1314-y | DOI Listing |
Curr Mol Med
January 2025
Department of Cardiology, Lishui People's Hospital, the Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China.
Background: Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with significant morbidity and mortality. Inflammation has been implicated in the pathogenesis of AF, but the causal relationship between specific inflammatory proteins and AF risk is not well established. This study aims to clarify this relationship using a bidirectional two-sample Mendelian Randomization (TSMR) approach.
View Article and Find Full Text PDFMol Ther
January 2025
Immune Health, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia; Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, New South Wales, Australia. Electronic address:
Vitronectin (VTN) is an important extracellular matrix protein in tissue remodeling, but its role in COPD is unknown. We show that VTN regulates tissue remodeling through urokinase plasminogen activator (uPA) signaling pathway in COPD. In human COPD airways and bronchoepithelial cells and the airways of mice with cigarette smoke (CS)-induced experimental COPD, VTN protein was not changed, but downstream uPA signaling was altered (increased plasminogen activator inhibitor-1, uPAR) that induced collagen and airway remodeling.
View Article and Find Full Text PDFCell Commun Signal
January 2025
Laboratory of Metabolism and Cancer Prevention, Department of Cell Biology & Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.
FGF21 regulates local and systemic metabolic homeostasis. High serum FGF21 was found in obesity, metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. The pathways linking obesity and breast cancer remain elusive.
View Article and Find Full Text PDFFront Cardiovasc Med
January 2025
Department of Cardiology, Liuzhou Workers' Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China.
Background: Fibroblasts in the fibrotic heart exhibit a heterogeneous biological behavior. The specific subsets of fibroblasts that contribute to progressive cardiac fibrosis remain unrevealed. Our aim is to identify the heart fibroblast (FB) subsets that most significantly promote fibrosis and the related critical genes as biomarkers for ischemic heart disease.
View Article and Find Full Text PDFHeliyon
January 2025
Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
The extracellular matrix (ECM) is a complex and dynamic three-dimensional network that functions as an architectural scaffold to maintain cardiac homeostasis. Important biochemical and mechanical signals associated with cell‒cell communication are provided via the reciprocal interaction between cells and the ECM. By converting mechanical cues into biochemical signals, the ECM regulates many cell processes, including migration, adhesion, growth, differentiation, proliferation, and apoptosis.
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