Department of Cardiovascular Disease IV, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, China.
Department of Cardiovascular Disease I, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, China.
Chem Biol Drug Des. 2024 Oct;104(4):e14628. doi: 10.1111/cbdd.14628.
As a key molecule for improving cardiovascular diseases, Apelin-13 was surveyed in this work to explain its actions in controlling inflammation, pyroptosis, and myocardial hypertrophy. First, mouse models with myocardial hypertrophy were established. Then, assessments were made on the pathological variation in the heart of mouse, on the cardiac functions, as well as on the expressions of cardiac hypertrophy markers (β-MHC, ANP, and BNP), inflammatory factors (TNF-α, COX2, IL-6, ICAM-1, and VCAM-1), myocardial cell pyroptosis markers (NLRP3, ASC, c-caspase-1, and GSDMD-N), and Hippo pathway proteins (p-YAP, YAP, LATS1, and p-LATS1) by HE staining, echocardiography scanning, and western blot tests separately. The expressions of such inflammatory factors as in myocardial tissue were acquired by ELISA. After inducing the phenotype of H9c2 cell hypertrophy by noradrenaline, we used CCK-8 kits to know about the activity of H9c2 cells treated with Apelin-13, and performed ɑ-actinin staining to measure the changes in volumes of such cells. As unraveled through this work, Apelin-13 refrained the activation of the Hippo pathway, which in turn attenuated the hypertrophy, inflammation, and pyroptosis of myocardial tissue and H9c2 cells. Hence, Apelin-13 can be considered as a target for hypertension treatment.
作为改善心血管疾病的关键分子,本研究考察了 Apelin-13 在控制炎症、细胞焦亡和心肌肥厚中的作用。首先,建立了心肌肥厚的小鼠模型。然后,通过 HE 染色、超声心动图扫描和 Western blot 分别评估小鼠心脏的病理变化、心脏功能以及心肌肥厚标志物(β-MHC、ANP 和 BNP)、炎症因子(TNF-α、COX2、IL-6、ICAM-1 和 VCAM-1)、心肌细胞焦亡标志物(NLRP3、ASC、c-caspase-1 和 GSDMD-N)和 Hippo 通路蛋白(p-YAP、YAP、LATS1 和 p-LATS1)的表达。通过 ELISA 获得心肌组织中炎症因子的表达。用去甲肾上腺素诱导 H9c2 细胞肥大表型后,用 CCK-8 试剂盒检测 Apelin-13 处理的 H9c2 细胞的活性,并用α-肌动蛋白染色测量细胞体积的变化。本研究揭示了 Apelin-13 抑制了 Hippo 通路的激活,从而减轻了心肌组织和 H9c2 细胞的肥大、炎症和细胞焦亡。因此,Apelin-13 可以被认为是治疗高血压的一个靶点。