Zhao Yanli, Zheng Qi, Gao Hanchao, Cao Mengtao, Wang Huiyun, Chang Rong, Zeng Changchun
Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen 518110, China.
School of Life Sciences, Shandong University, Qingdao 266237, China.
iScience. 2021 Feb 25;24(3):102233. doi: 10.1016/j.isci.2021.102233. eCollection 2021 Mar 19.
Cardiac hypertrophy is an adaptive response to all forms of heart disease, including hypertension, myocardial infarction, and cardiomyopathy. Cyclooxygenase-2 (COX-2) overexpression results in inflammatory response, cardiac cell apoptosis, and hypertrophy in adult heart after injury. However, immune response-mediated cardiac hypertrophy and fibrosis have not been well documented in injured neonatal heart. This study showed that cardiac hypertrophy and fibrosis are significantly attenuated in celecoxib (a selective COX-2 inhibitor)-treated P8 ICR mice after cryoinjury. Molecular and cellular profiling of immune response shows that celecoxib inhibits the production of cytokines and the expression of adhesion molecular genes, increases the recruitment of M1-like macrophage at wound site, and alleviates cardiac hypertrophy and fibrosis. Furthermore, celecoxib administration improves cardiac function at 4 weeks after injury. These results demonstrate that COX-2 inhibition promotes the recruitment of M1-like macrophages during early wound healing, which may contribute to the suppression of cardiac hypertrophy and fibrosis after injury.
心脏肥大是对包括高血压、心肌梗死和心肌病在内的所有形式心脏病的一种适应性反应。环氧合酶-2（COX-2）的过度表达会导致炎症反应、心脏细胞凋亡以及成年心脏损伤后的肥大。然而，免疫反应介导的心脏肥大和纤维化在新生心脏损伤中尚未得到充分记录。本研究表明，在冷冻损伤后，塞来昔布（一种选择性COX-2抑制剂）处理的P8 ICR小鼠的心脏肥大和纤维化显著减轻。免疫反应的分子和细胞分析表明，塞来昔布抑制细胞因子的产生和黏附分子基因的表达，增加伤口部位M1样巨噬细胞的募集，并减轻心脏肥大和纤维化。此外，给予塞来昔布可在损伤后4周改善心脏功能。这些结果表明，COX-2抑制在早期伤口愈合过程中促进M1样巨噬细胞的募集，这可能有助于抑制损伤后的心脏肥大和纤维化。
