ArticleCirculation research2011
Thrombospondin-4 is required for stretch-mediated contractility augmentation in cardiac muscle.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
59 citing papers in PubMed, 93 citations in OpenAlex.
- Mechanobiology of Matricellular Proteins in Bladder Cancer: A Narrative Review and Bioinformatics Analysis.Biomolecules · 2026Review
- THBS4 Regulates Pulmonary Hypertension via TGF-β/SMAD2 Signaling.Hypertension (Dallas, Tex. : 1979) · 2026Article
- A proteomic signature of vascular dysfunction linked to tauopathy and degeneration in the aging brain.bioRxiv : the preprint server for biology · 2025Article
- The mechanobiology of extracellular matrix: a focus on thrombospondins.Cell communication and signaling : CCS · 2025Review
- Genomic analysis reveals population structure and selection signatures in plateau dairy cattle.BMC genomics · 2025Article
- The Heart Is a Smart Pump: Mechanotransduction Mechanisms of the Frank-Starling Law and the Anrep Effect.Annual review of physiology · 2025Review
- Fibroblast-specific TGF-β signaling mediates cardiac dysfunction, fibrosis, and hypertrophy in obese diabetic mice.Cardiovascular research · 2024Article
- Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix.International journal of experimental pathology · 2024Review
- Thrombospondin-4 deletion does not exacerbate muscular dystrophy in β-sarcoglycan-deficient and laminin α2 chain-deficient mice.Scientific reports · 2024Article
- The secretome as a biomarker and functional agent in heart failure.The journal of cardiovascular aging · 2023Article
- Plasma proteomic profiling in postural orthostatic tachycardia syndrome (POTS) reveals new disease pathways.Scientific reports · 2022Article
- THBS4/integrin α2 axis mediates BM-MSCs to promote angiogenesis in gastric cancer associated with chronicAging · 2021Article
- Emergence of Mechano-Sensitive Contraction Autoregulation in Cardiomyocytes.Life (Basel, Switzerland) · 2021Article
- Indirect podocyte injury manifested in a partial podocytectomy mouse model.American journal of physiology. Renal physiology · 2021Article
- COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis.International journal of molecular sciences · 2021Article
- Thrombospondin-4 Is a Soluble Dermal Inflammatory Signal That Selectively Promotes Fibroblast Migration and Keratinocyte Proliferation for Skin Regeneration and Wound Healing.Frontiers in cell and developmental biology · 2021Article
- Tendon Extracellular Matrix Assembly, Maintenance and Dysregulation Throughout Life.Advances in experimental medicine and biology · 2021Review
- The Attenuating Effect of Low-Intensity Pulsed Ultrasound on Hypoxia-Induced Rat Chondrocyte Damage in TMJ Osteoarthritis Based on TMT Labeling Quantitative Proteomic Analysis.Frontiers in pharmacology · 2021Article
- Quantitative Proteomics of Human Heart Samples CollectedMolecular & cellular proteomics : MCP · 2020Article
- Thrombospondin-4 induces prolongation of action potential duration in rat isolated ventricular myocytes.The Journal of veterinary medical science · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
rationaleOne of the physiological mechanisms by which the heart adapts to a rise in blood pressure is by augmenting myocyte stretch-mediated intracellular calcium, with a subsequent increase in contractility. This slow force response was first described over a century ago and has long been considered compensatory, but its underlying mechanisms and link to chronic adaptations remain uncertain. Because levels of the matricellular protein thrombospondin-4 (TSP4) rapidly rise in hypertension and are elevated in cardiac stress overload and heart failure, we hypothesized that TSP4 is involved in this adaptive mechanism.
objectiveTo determine the mechano-transductive role that TSP4 plays in cardiac regulation to stress. METHODS AND
resultsIn mice lacking TSP4 (Tsp4⁻/⁻), hearts failed to acutely augment contractility or activate stretch-response pathways (ERK1/2 and Akt) on exposure to acute pressure overload. Sustained pressure overload rapidly led to greater chamber dilation, reduced function, and increased heart mass. Unlike controls, Tsp4⁻/⁻ cardiac trabeculae failed to enhance contractility and cellular calcium after a stretch. However, the contractility response was restored in Tsp4⁻/⁻ muscle incubated with recombinant TSP4. Isolated Tsp4⁻/⁻ myocytes responded normally to stretch, identifying a key role of matrix-myocyte interaction for TSP4 contractile modulation.
conclusionThese results identify TSP4 as myocyte-interstitial mechano-signaling molecule central to adaptive cardiac contractile responses to acute stress, which appears to play a crucial role in the transition to chronic cardiac dilatation and failure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.