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Updated: May 20, 2026
Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes
Published on: September 24, 2013
High-mobility group box 1 induces calcineurin-mediated cell hypertrophy in neonatal rat ventricular myocytes
Fei-fei Su1, Miao-qian Shi, Wan-gang Guo
1Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Insights
High-mobility group box 1 (HMGB1) protein can cause cardiac hypertrophy in cardiomyocytes. This occurs through the activation of calcineurin, a key signaling pathway in cardiac remodeling.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cell Biology
Background:
- Cardiac hypertrophy is a significant risk factor for cardiovascular disease.
- High-mobility group box 1 (HMGB1) protein is implicated in cardiac remodeling, but its role in hypertrophy is unclear.
Purpose of the Study:
- To determine if HMGB1 can induce cardiomyocyte hypertrophy.
- To elucidate the molecular mechanisms by which HMGB1 affects cardiac hypertrophy.
Main Methods:
- Primary rat cardiomyocytes were treated with recombinant HMGB1.
- Analysis included atrial natriuretic peptide (ANP) and calcineurin A expression via Western blot and RT-PCR.
- Calcineurin activity was measured biochemically; cyclosporin A was used to assess pathway involvement.
Main Results:
- HMGB1 treatment resulted in cardiomyocyte hypertrophy, evidenced by increased ANP expression and protein synthesis.
- HMGB1 elevated calcineurin activity and calcineurin A protein levels.
- Cyclosporin A partially blocked HMGB1-induced hypertrophy.
Conclusions:
- HMGB1 induces cardiomyocyte hypertrophy.
- The calcineurin signaling pathway is a key mediator of HMGB1-induced cardiac hypertrophy.
Abstract:
Cardiac hypertrophy is an independent predictor of cardiovascular morbidity and mortality. In recent years, evidences suggest that high-mobility group box 1 (HMGB1) protein, an inflammatory cytokine, participates in cardiac remodeling; however, the involvement of HMGB1 in the pathogenesis of cardiac hypertrophy remains unknown. The aim of this study was to investigate whether HMGB1 is sufficient to induce cardiomyocyte hypertrophy and to identify the possible mechanisms underlying the hypertrophic response. Cardiomyocytes isolated from 1-day-old Sprague-Dawley rats were treated with recombinant HMGB1, at concentrations ranging from 50 ng/mL to 200 ng/mL. After 24 hours, cardiomyocytes were processed for the evaluation of atrial natriuretic peptide (ANP) and calcineurin A expression. Western blot and real-time RT-PCR was used to detect protein and mRNA expression levels, respectively. The activity of calcineurin was also evaluated using a biochemical enzyme assay. HMGB1 induced cardiomyocyte hypertrophy, characterized by enhanced expression of ANP, and increased protein synthesis. Meanwhile, increased calcineurin activity and calcineurin A protein expression were observed in cardiomyocytes preconditioned with HMGB1. Furthermore, cyclosporin A pretreatment partially inhibited the HMGB1-induced cardiomyocyte hypertrophy. Our findings suggest that HMGB1 leads to cardiac hypertrophy, at least in part through activating calcineurin.
