Tenascin-C drives cardiovascular dysfunction in a mouse model of diabetic cardiomyopathy
Authors' conclusion
Our findings indicate that in diabetes, TNC contributes to cardiac contractile dysfunction, myocardial fibrosis, oxidative stress, inflammation, and metabolic disturbances in diabetic mouse heart. These results implicate the potential of TNC inhibition as a novel therapeutic approach for treating DCM.
Study context
- Population
- Adult male wild-type (WT) and TNC knockout (TNC-KO) mice with streptozotocin-induced diabetes (50 mg/kg, 5 consecutive days); cardiomyocytes and cardiac fibroblasts; plasma Tenascin-C (TNC) in HF patients and T2D cohorts
- Comparison
- TNC-KO vs WT diabetic mice
- Outcome
- Cardiac and vascular function in diabetic mice
- Follow-up
- 18 weeks
Methodological detailsmouse model, streptozotocin-induced diabetes, knockout
- Mouse model
- Streptozotocin-induced diabetes
- Knockout
Main finding
As reported in the abstract
18 weeks
- TNC-KO diabetic mice showed preserved LV systolic and diastolic function vs WT diabetic animals
- Significantly reduced cardiac fibrosis in TNC-KO vs WT diabetic mice
- Mitigated endothelial dysfunction in TNC-KO vs WT diabetic mice
- TNC-KO cardiomyocytes developed less stiffness (Fpassive) vs diabetic WT
Further findings
TNC expression under high glucose (30 mM)
- High glucose stress led to a significant increase in TNC expression in mouse cardiomyocytes and human cardiac fibroblasts
Recombinant human TNC in cardiomyocytes
- Recombinant human TNC promoted pro-inflammatory and oxidative stress markers
RNA-sequencing
- Role of TNC involved p53 signaling and Serpin1k, Ccn1, Cpt1a and Slc27a1 pathways
Plasma TNC in humans
- Plasma TNC significantly elevated in HF patients, irrespective of diabetes status, vs healthy individuals
Original publication
Tenascin-C drives cardiovascular dysfunction in a mouse model of diabetic cardiomyopathy. Cardiovasc Diabetol. Published 31 May 2025. doi:10.
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