The Effects of Extracellular Vesicles Derived from Krüppel-Like Factor 2 Overexpressing Endothelial Cells on the Regulation of Cardiac Inflammation in the Dilated Cardiomyopathy

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2022 Feb 10

PMID 35139878

Authors

Wenfeng Zhang

Ziwei Chen

Shuaihua Qiao

Siyuan Chen

Hongyan Zheng

Xuan Wei

Qiaoling Li

Biao Xu

Wei Huang

Affiliations

Soon will be listed here.

Abstract

Background: Dilated cardiomyopathy (DCM) is one of the common causes of heart failure. Myocardial injury triggers an inflammatory response and recruits immune cells into the heart. High expression of Krüppel-like factor 2 (KLF2) in endothelial cells (ECs) potentially exerts an anti-inflammatory effect. However, the role of extracellular vesicles (EVs) from KLF2-overexpressing ECs (KLF2-EVs) in DCM remains unclear.

Methods And Results: EVs were separated from the supernatant of KLF2-overexpressing ECs by gradient centrifugation. Mice were repeatedly administered low-dose doxorubicin (DOX) and then received KLF2-EVs through an intravenous injection. Treatment with KLF2-EVs prevented doxorubicin-induced left ventricular dysfunction and reduced the recruitment of Ly6 Mo/Mø in the myocardium. We used flow cytometry to detect Ly6 monocytes in bone marrow and spleen tissues and to elucidate the mechanisms underlying this beneficial effect. KLF2-EVs increased the retention of Ly6C monocytes in the bone marrow but not in the spleen tissue. KLF2-EVs also significantly downregulated C-C chemokine receptor 2 (CCR2) protein expression in cells from the bone marrow.

Conclusions: EVs derived from KLF2-overexpressing ECs reduced cardiac inflammation and ameliorated left ventricular dysfunction in DCM mice by targeting the CCR2 protein to inhibit Ly6C monocyte mobilization from the bone marrow.

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