Li Xiao-Li, Yu Fei, Li Bao-Ying, Fu Chun-Li, Yu Xin, Xu Mei, Cheng Mei, Gao Hai-Qing
Department of Drug Purchase and Supply, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong Province, 250012, China.
Department of Geriatric Medicine, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong Province, 250012, China.
Cell Biol Int. 2020 Jan;44(1):268-277. doi: 10.1002/cbin.11229. Epub 2019 Sep 18.
The progression of diabetic cardiomyopathy is related to cardiomyocyte dysfunction and apoptosis. Our previous studies showed that asporin (ASPN) was significantly increased in the myocardium of db/db mice through proteomics, and grape seed procyanidin B2 (GSPB2) significantly inhibited the expression of ASPN in the heart of db/db mice. We report here that ASPN played a critical role in glycated low-density lipoproteins (gly-LDL) induced-cardiomyocyte apoptosis. We found that gly-LDL upregulated ASPN expression. ASPN increased H9C2 cardiomyocyte apoptosis with down-regulation of Bcl-2, upregulation of transforming growth factor-β1, Bax, collagen III, fibronectin, and phosphorylation of smad2 and smad3. However, GSPB2 treatment reversed ASPN-induced impairments in H9C2 cardiomyocytes. These results provide evidence for the cardioprotective action of GSPB2 against ASPN injury, and thus suggest a new target for fighting against diabetic cardiomyopathy.
糖尿病性心肌病的进展与心肌细胞功能障碍和凋亡有关。我们之前的研究通过蛋白质组学表明，在db/db小鼠的心肌中，阿spor蛋白（ASPN）显著增加，而葡萄籽原花青素B2（GSPB2）显著抑制db/db小鼠心脏中ASPN的表达。我们在此报告，ASPN在糖化低密度脂蛋白（gly-LDL）诱导的心肌细胞凋亡中起关键作用。我们发现gly-LDL上调了ASPN的表达。ASPN增加了H9C2心肌细胞凋亡，同时下调了Bcl-2，上调了转化生长因子-β1、Bax、胶原蛋白III、纤连蛋白以及smad2和smad3的磷酸化。然而，GSPB2处理逆转了ASPN对H9C2心肌细胞造成的损伤。这些结果为GSPB2对ASPN损伤的心脏保护作用提供了证据，从而为对抗糖尿病性心肌病提出了一个新靶点。
