Department of Cardiovascular Medicine, The First Hospital of China Medical University, Shenyang, People's Republic of China.
Bioengineered. 2022 Feb;13(2):2597-2609. doi: 10.1080/21655979.2021.2019869.
Essential hypertension (EH) represents a major risk factor for stroke, myocardial infarction, and heart failure. Dysregulated proliferation and migration of vascular smooth muscle cells (VSMCs) play an important role in pathogenesis of EH. This study aims to investigate the effect of Chromodomain Helicase DNA Binding Protein 1-Like (CHD1L) on Angiotensin II (AngII)-induced VSMCs injury and reveal the underlying mechanism. The expression of CHD1L in EH patients was determined by bioinformatics analysis, and then it was silenced in AngII-induced VSMCs to detect the changes in cellular functions including proliferation, migration, invasion and phenotypic switching via CCK-8, EDU staining, wound healing, transwell and Western blot assays, respectively. Inflammation and oxidative stress were also measured by detecting related markers via commercial kits. After confirming the binding sites between forkhead box O3A (FOXO3a) and CHD1L and their negative association by bioinformatics analysis, FOXO3a was further silenced, and the cellular functions were assessed again to reveal the underlying mechanism. Results showed that CHD1L was highly expressed in EH, and interference of CHD1L suppressed the proliferation, migration, invasion and phenotypic switching in VSMCs. Inflammation and oxidative stress were also restrained by CHD1L knockdown. After validating the negative role of FOXO3a in regulating CHD1L, it was found that FOXO3a abrogated the effect of CHD1L knockdown on the cellular functions of AngII-induced VSMCs. In conclusion, FOXO3a suppresses the proliferation and migration of AngII-induced VSMCs by down-regulating CHD1L.
原发性高血压(EH)是中风、心肌梗死和心力衰竭的主要危险因素。血管平滑肌细胞(VSMCs)的增殖和迁移失调在EH 的发病机制中起着重要作用。本研究旨在探讨染色质解旋酶 DNA 结合蛋白 1 样蛋白(CHD1L)对血管紧张素 II(AngII)诱导的 VSMCs 损伤的影响，并揭示其潜在机制。通过生物信息学分析确定 EH 患者中 CHD1L 的表达，然后在 AngII 诱导的 VSMCs 中沉默 CHD1L，通过 CCK-8、EDU 染色、划痕愈合、Transwell 和 Western blot 测定分别检测细胞功能的变化，包括增殖、迁移、侵袭和表型转化。通过商业试剂盒检测相关标志物来测量炎症和氧化应激。在通过生物信息学分析确认叉头框 O3A(FOXO3a)和 CHD1L 之间的结合位点及其负相关关系后，进一步沉默 FOXO3a，并再次评估细胞功能以揭示潜在机制。结果表明，CHD1L 在 EH 中高表达，干扰 CHD1L 抑制了 VSMCs 的增殖、迁移、侵袭和表型转化。炎症和氧化应激也被 CHD1L 敲低所抑制。验证了 FOXO3a 在调节 CHD1L 中的负作用后，发现 FOXO3a 消除了 CHD1L 敲低对 AngII 诱导的 VSMCs 细胞功能的影响。综上所述，FOXO3a 通过下调 CHD1L 抑制 AngII 诱导的 VSMCs 的增殖和迁移。
