Background and aims: It is commonly believed that diabetes is an important contributor to heart failure (HF) development. However, the detail effect of diabetogenesis on HF is controversy: both beneficial and harmful roles were reported. In the present study, we aim to explore the unambiguous action of diabetes on chronic HF progression and the underlying mechanism.
Methods: Diabetes and myocardial infarction (MI) were induced by streptozotocin (STZ) injection and left-sided thoracotomy and left anterior descending coronary artery (LAD) ligation, respectively. Pyridoxamine was used as the antagonist of advanced glycation end products (AGEs). Adult male SD rats were assigned to 5 groups: Sham; MI; Diabetes (D); Diabetes+MI (DMI) and DMI+pyridoxamine (DMI+P). Animals were sacrificed at the end of 12weeks. The comparison of LV myocardium was made between border zone from MI or DMI animals and control LV tissues from sham-operated animals. Cardiomyocytes and dendritic cells were prepared from the Sprague-Dawley rats and cocultured in the presence or absence of AGEs.
Results: DMI group showed highest level of AGEs and inflammatory markers, which were significantly reduced in the presence of pyridoxamine. In vitro experiment disclosed AGEs could stimulate DCs differentiation and promote cytokines production, finally upregulated hypertrophy-related genes expression in cardiocytes. Intervention DCs differentiation was sufficient to improve cardiocytes morphology.
Conclusion: Our results clearly demonstrate that diabetes would promote chronic HF progression at least in part through stimulating DCs differentiation and series downstream inflammatory responses induced by AGEs.
Keywords: Advanced glycation end product; Dendritic cells; Heart failure; NF-κB signaling.
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