Liu Hainiang, Wang Haoren, Cheng Dong, Wang Qinfu, Pei Zuowei, Zhu Ning, Fang Weiyi, Yu Qin
Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University Dalian 116001 China
Medical College, Dalian University Dalian 116622 China.
RSC Adv. 2019 May 7;9(25):14321-14330. doi: 10.1039/c9ra01190k.
Excessive tumor necrosis factor-α (TNF-α) could enhance cell death and aggravate left ventricular remodeling and myocardial dysfunction. A disintegrin and metalloproteinase-17 (ADAM17), an important maturation regulator of TNF-α, might be involved in the aging-associated ventricular remodeling. The present study observed myocardial ADAM17 expression in young and aged rats and explored the association between cardiac structure/function and expression of ADAM17 in 6 month-old ( = 10, young group) and 24 month-old SD rats ( = 10, old group). The body, heart weight and heart weight/body weight ratio of rats in the old group were all significantly increased compared to that in the young group ( < 0.05). The left ventricular systolic end-diameter and end-diastolic diameters were significantly enlarged in the old group compared to the young group ( < 0.05), while the systolic function index including the left ventricular ejection fraction and left ventricular fractional shortening were similar between the two groups. The peak mitral flow velocity ()/peak mitral annulus velocity (') ratio was significantly higher in the old group than in the young group ( < 0.05). Histological examination showed more damage of cardiomyocytes, interstitial collagen deposition and inflammatory cell infiltration in the old group. Immunohistochemistry examination showed that myocardial TNF-α expression was mainly located in cardiomyocytes and was significantly higher in the old group than in the young group ( < 0.05). The protein expression of myocardial ADAM17 detected by western blot was significantly higher in the old group than in the young group ( < 0.05), while TIMP-3 expression was similar between the two groups. The present study suggested that ADAM17 and inflammation might play an important role in aging-related myocardial remodeling through regulating TNF-α.
过量的肿瘤坏死因子-α（TNF-α）可增强细胞死亡，并加重左心室重构和心肌功能障碍。作为TNF-α的重要成熟调节因子，解聚素和金属蛋白酶-17（ADAM17）可能参与了与衰老相关的心室重构。本研究观察了年轻和老年大鼠心肌中ADAM17的表达，并探讨了6月龄（n = 10，年轻组）和24月龄SD大鼠（n = 10，老年组）心脏结构/功能与ADAM17表达之间的关联。与年轻组相比，老年组大鼠的体重、心脏重量及心脏重量/体重比均显著增加（P < 0.05）。与年轻组相比，老年组左心室收缩末期内径和舒张末期内径显著增大（P < 0.05），而两组间包括左心室射血分数和左心室缩短分数在内的收缩功能指标相似。老年组二尖瓣血流速度峰值（E）/二尖瓣环速度峰值（A）比值显著高于年轻组（P < 0.05）。组织学检查显示，老年组心肌细胞损伤更多，间质胶原沉积和炎性细胞浸润更明显。免疫组织化学检查显示心肌TNF-α表达主要位于心肌细胞，老年组显著高于年轻组（P < 0.05）。蛋白质印迹法检测显示，老年组心肌ADAM17的蛋白表达显著高于年轻组（P < 0.05）,而两组间TIMP-3表达相似。本研究提示，ADAM17和炎症可能通过调节TNF-α在衰老相关的心肌重构中发挥重要作用。
