Neutrophil-like cell membrane-coated siRNA of lncRNA AABR07017145.1 therapy for cardiac hypertrophy via inhibiting ferroptosis of CMECs

Pilong Shi; Minghui Li; Chao Song; Hanping Qi; Lina Ba; Yonggang Cao; Meitian Zhang; Yawen Xie; Jing Ren; Jiabi Wu; Ping Ren; Hongli Sun

doi:10.1016/j.omtn.2021.10.024

Neutrophil-like cell membrane-coated siRNA of lncRNA AABR07017145.1 therapy for cardiac hypertrophy via inhibiting ferroptosis of CMECs

Mol Ther Nucleic Acids. 2021 Nov 3:27:16-36. doi: 10.1016/j.omtn.2021.10.024. eCollection 2022 Mar 8.

Authors

Pilong Shi¹, Minghui Li², Chao Song¹, Hanping Qi¹, Lina Ba¹, Yonggang Cao¹, Meitian Zhang¹, Yawen Xie¹, Jing Ren¹, Jiabi Wu¹, Ping Ren¹, Hongli Sun¹

Affiliations

¹ Department of Pharmacology, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, China.
² Department of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, China.

Abstract

Cardiac microvascular dysfunction is associated with cardiac hypertrophy and can eventually lead to heart failure. Dysregulation of long non-coding RNAs (lncRNAs) has recently been recognized as one of the key mechanisms involved in cardiac hypertrophy. However, the potential roles and underlying mechanisms of lncRNAs in cardiac microvascular dysfunction have not been explicitly delineated. Our results confirmed that cardiac microvascular dysfunction was related to cardiac hypertrophy and ferroptosis of cardiac microvascular endothelial cells (CMECs) occurred during cardiac hypertrophy. Using a combination of in vivo and in vitro studies, we identified a lncRNA AABR07017145.1, named as lncRNA AAB for short, and revealed that lncRNA AAB was upregulated in the hearts of cardiac hypertrophy rats as well as in the Ang II-induced CMECs. Importantly, we found that lncRNA AAB sponged and sequestered miR-30b-5p to induce the imbalance of MMP9/TIMP1, which enhanced the activation of transferrin receptor 1 (TFR-1) and then eventually led to the ferroptosis of CMECs. Moreover, we have developed a delivery system based on neutrophil membrane (NM)-camouflaged mesoporous silica nanocomplex (MSN) for inhibition of cardiac hypertrophy, indicating the potential role of silenced lncRNA AAB (si-AAB) and overexpressed miR-30b-5p as the novel therapy for cardiac hypertrophy.

Keywords: cardiac hypertrophy; cardiac microvascular endothelial cell; ferroptosis; lncRNA AABR07017145.1; miR-30b-5p; neutrophil membrane-camouflaged nanocomplex.