ArticlePloS one2018
The extracellular matrix proteoglycan fibromodulin is upregulated in clinical and experimental heart failure and affects cardiac remodeling.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- A Meta-Analysis Approach to Gene Regulatory Network Inference Identifies Key Regulators of Cardiovascular Diseases.International journal of molecular sciences · 2024Pooled it
- O-GlcNAcylation as a Metabolic Integrator in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2026Review
- Fibromodulin positively regulated by Androgen Receptor, promotes prostate cancer progression via the PI3K/AKT signaling pathway and epithelial-medenchymal transition.Molecular biology reports · 2026Article
- Combining genome and tissue engineering for next-generation human biomimetics.Stem cells translational medicine · 2025Article
- Sublethal Doxorubicin Promotes Extracellular Vesicle Biogenesis in A375 Melanoma Cells: Implications for Vesicle-Loaded TGF-β-Mediated Cancer Progression and Cardiovascular Pathophysiology.International journal of molecular sciences · 2025Article
- The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Nanoscale piezoelectric patches preserve electrical integrity of infarcted hearts.Materials today. Bio · 2025Article
- A secretome atlas of cardiac fibroblasts from healthy and infarcted mouse hearts.Communications biology · 2025Article
- The role of fibromodulin in myocardial fibrosis in a diabetic cardiomyopathy rat model.FEBS open bio · 2025Article
- Comprehensive bioinformatics analysis of hub genes in ischemic heart failure and atrial fibrillation.Frontiers in cardiovascular medicine · 2025Article
- Heart failure: mechanistic insights and precision therapeutic strategies.Frontiers in cardiovascular medicine · 2025Review
- Preliminary exploration of potential biomarkers for heart failure and bipolar disorder: an exploratory study based on bioinformatics.Frontiers in psychiatry · 2025Article
- Identification of fibrosis-associated biomarkers in heart failure and human cancers.Journal of translational medicine · 2024Article
- Protein glycosylation in cardiovascular health and disease.Nature reviews. Cardiology · 2024Review
- Age-dependent changes in collagen crosslinks reduce the mechanical toughness of human meniscus.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2024Article
- HAPLN1 knockdown inhibits heart failure development via activating the PKA signaling pathway.BMC cardiovascular disorders · 2024Article
- Comparative analysis of ventricular stiffness across species.Physiological reports · 2024Review
- Effect of Bioactive Glasses and Basic Fibroblast Growth Factor on Dental Pulp Cells.Journal of functional biomaterials · 2023Article
- The secretome atlas of two mouse models of progeria.Aging cell · 2023Article
- Downregulation of fibromodulin attenuates inflammatory signaling and atrial fibrosis in spontaneously hypertensive rats with atrial fibrillation via inhibiting TLR4/NLRP3 signaling pathway.Immunity, inflammation and disease · 2023Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pressure overload of the heart leads to cardiac remodeling that may progress into heart failure, a common, morbid and mortal condition. Increased mechanistic insight into remodeling is instrumental for development of novel heart failure treatment. Cardiac remodeling comprises cardiomyocyte hypertrophic growth, extracellular matrix alterations including fibrosis, and inflammation. Fibromodulin is a small leucine-rich proteoglycan that regulates collagen fibrillogenesis. Fibromodulin is expressed in the cardiac extracellular matrix, however its role in the heart remains largely unknown. We investigated fibromodulin levels in myocardial biopsies from heart failure patients and mice, subjected fibromodulin knock-out (FMOD-KO) mice to pressure overload by aortic banding, and overexpressed fibromodulin in cultured cardiomyocytes and cardiac fibroblasts using adenovirus. Fibromodulin was 3-10-fold upregulated in hearts of heart failure patients and mice. Both cardiomyocytes and cardiac fibroblasts expressed fibromodulin, and its expression was increased by pro-inflammatory stimuli. Without stress, FMOD-KO mice showed no cardiac phenotype. Upon aortic banding, left ventricles of FMOD-KO mice developed mildly exacerbated hypertrophic remodeling compared to wild-type mice, with increased cardiomyocyte size and altered infiltration of leukocytes. There were no differences in mortality, left ventricle dilatation, dysfunction or expression of heart failure markers. Although collagen amount and cross-linking were comparable in FMOD-KO and wild-type, overexpression of fibromodulin in cardiac fibroblasts in vitro decreased their migratory capacity and expression of fibrosis-associated molecules, i.e. the collagen-cross linking enzyme lysyl oxidase, transglutaminase 2 and periostin. In conclusion, despite a robust fibromodulin upregulation in clinical and experimental heart failure, FMOD-KO mice showed a relatively mild hypertrophic phenotype. In cultured cardiac fibroblasts, fibromodulin has anti-fibrotic effects.
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