ArticleMolecular medicine (Cambridge, Mass.)2014
Human myocardium releases heat shock protein 27 (HSP27) after global ischemia: the proinflammatory effect of extracellular HSP27 through toll-like receptor (TLR)-2 and TLR4.
Article in Molecular medicine (Cambridge, Mass.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 122 citations in OpenAlex.
- Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients.Clinical nutrition (Edinburgh, Scotland) · 2020Trial
- Effect of helium pre- or postconditioning on signal transduction kinases in patients undergoing coronary artery bypass graft surgery.Journal of translational medicine · 2016Trial
- Sterile Inflammation and Cell Death Pathways in Liver Ischemia-Reperfusion Injury: A Review and Perspective.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Unveiling the Immunostimulatory Potential of the HSPA1A Mini-Chaperones Compared to the HSPA1A and HSP27 Chaperones: In Silico and In Vitro Insights for Vaccine Development.The protein journal · 2025Article
- Evidence that extracellular HSPB1 contributes to inflammation in alcohol-associated hepatitis.Hepatology communications · 2025Article
- Cellular Stress Responses and Associated Diseases: A Focus on Heat Shock Proteins.Cell biochemistry and biophysics · 2025Review
- Overexpression of the human heat shock protein B1 alters obesity-related metabolic changes in a sex-dependent manner in a mouse model of metabolic syndrome.Biology of sex differences · 2025Article
- Cannabinoids as Multitarget Drugs for the Treatment of Autoimmunity in Glaucoma.ACS pharmacology & translational science · 2025Review
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Unveiling the role of exercise in modulating plasma heat shock protein 27 levels: insights for exercise immunology and cardiovascular health.Molecular and cellular biochemistry · 2025Review
- Intermittent fasting reduces glaucomatous damage in an HSP27 autoimmune mouse model.Frontiers in cellular neuroscience · 2025Article
- Ischemic cardiac stromal fibroblast-derived protein mediators in the infarcted myocardium and transcriptomic profiling at single cell resolution.Functional & integrative genomics · 2024Article
- Reactive astrocytes secrete the chaperone HSPB1 to mediate neuroprotection.Science advances · 2024Article
- Analysis and validation of serum biomarkers in brucellosis patients through proteomics and bioinformatics.Frontiers in cellular and infection microbiology · 2024Article
- The biphasic role of Hspb1 on ferroptotic cell death in Parkinson's disease.Theranostics · 2024Article
- Toll-like receptor 4 in pancreatic damage and immune infiltration in acute pancreatitis.Frontiers in immunology · 2024Review
- The role of heat shock proteins in the pathogenesis of heart failure (Review).International journal of molecular medicine · 2023Review
- IGFBPL1 is a master driver of microglia homeostasis and resolution of neuroinflammation in glaucoma and brain tauopathy.Cell reports · 2023Article
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17 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The myocardial inflammatory response contributes to cardiac functional injury associated with heart surgery obligating global ischemia/reperfusion (I/R). Toll-like receptors (TLRs) play an important role in the mechanism underlying myocardial I/R injury. The aim of this study was to examine the release of small constitutive heat shock proteins (HSPs) from human and mouse myocardium after global ischemia and examine the role of extracellular small HSP in myocardial injury. HSP27 release was assessed by enzyme-linked immunosorbent assay. Anti-HSP27 was applied to evaluate the role of extracellular HSP27 in the postischemic inflammatory response and functional injury in mouse hearts. Isolated hearts and cultured coronary vascular endothelial cells were exposed to recombinant HSP27 to determine its effect on proinflammatory signaling and production of proinflammatory mediators. HSP27 levels were markedly elevated in coronary sinus blood of patients and in coronary effluent of mouse hearts after global ischemia. Neutralizing extracellular HSP27 suppressed myocardial nuclear factor (NF)-κB activation and interleukin (IL)-6 production and improved cardiac function in mouse hearts. Perfusion of HSP27 to mouse hearts induced NF-κB activation and IL-6 production and depressed contractility. Further, recombinant HSP27 induced NF-κB phosphorylation and upregulated monocyte chemoattractant protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1 production in both human and mouse coronary vascular endothelial cells. TLR2 knockout (KO) or TLR4 mutation abolished NF-κB phosphorylation and reduced MCP-1 and ICAM-1 production induced by extracellular HSP27 in endothelial cells. In conclusion, these results show that the myocardium releases HSP27 after global ischemia and that extracellular HSP27 is proinflammatory and contributes to the inflammatory mechanism of myocardial functional injury. Both TLR2 and TLR4 are involved in mediating the proinflammatory effect of extracellular HSP27.
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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.