主催: 公益社団法人日本薬理学会
会議名: 第97回日本薬理学会年会
回次: 97
開催地: 神戸
開催日: 2023/12/14 - 2023/12/16
Background: Diabetic cardiomyopathy (DCM) is a complication of diabetes that results in pathological cardiac hypertrophy and fibrosis, leading to cardiac dysfunction. DCM also induces cardiac senescence. Epigenetic changes are involved in cellular senescence. However, there is no suitable DCM model that can be created in a short period of time. The purpose of this study is to establish a mouse model of DCM and elucidate the cardiac epigenetic change using the animals.
Methods and Results: Cardiac myoblast H9c2 cells were treated with AGEs (100 or 200 μg/mL). AGEs increased the protein levels of p53 and γ-H2AX as well as the gene expression levels of p21 and p53. Next, we examined a mouse model of type 2 diabetes. C57BL6/N mice (8-week-old, male) were fed a high-fat diet (HFD) and L-NAME (1 g/L) for 4 weeks, followed by daily injections of streptozotocin (STZ) (50 mg/kg/day) for 5 days and sacrificed after another 4 weeks. Picrosirius red staining showed that cardiac fibrosis was increased in L-NAME+HFD+STZ (LHS) mice. LHS mice showed increased gene expression levels of inflammatory cytokines, fibrosis-related genes, and senescence markers. Acetylation and crotonylation levels of histone H3K9 were enhanced in LHS mice.
Conclusion: We established a novel mouse model of DCM, and DCM might be regulated by epigenetic mechanisms.
