LMK235 ameliorates inflammation and fibrosis after myocardial infarction by inhibiting LSD1-related pathway

doi:10.1038/s41598-024-74887-3

科研成果详情

题名	LMK235 ameliorates inflammation and fibrosis after myocardial infarction by inhibiting LSD1-related pathway
作者	Lv, Fangzhou 1,2; Xie, Laidi 1; Li, Lei 2; Lin, Jiafeng2
发表日期	2024-10-08
发表期刊	Scientific Reports 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Myocardial infarction HDAC4 HDAC5 LSD1 NF-kappa B pathway Smad2/3 pathway
其他关键词	PROTEIN-KINASE-D ; HISTONE DEACETYLASE 5 ; CLASS-I ; ACTIVATION ; HDAC4 ; PHOSPHORYLATION ; DIFFERENTIATION ; PROLIFERATION ; TRANSCRIPTION ; FIBROBLASTS
摘要	Background: Histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5) are two isoforms of class IIa HDACs, and LMK235 is an HDAC inhibitor with higher selectivity for HDAC4/5. This study aimed to explore the expression and subcellular localization of HDAC4/5 and determine the mechanisms underlying the impact of LMK235 on ventricular remodelling post-MI. Methods: The MI model was established by left anterior descending branch (LAD) ligation, and LMK235 or vehicle was intraperitoneally injected daily for 21 days. Cardiac function was determined by echocardiography. Inflammation was evaluated by HE staining and measuring inflammatory cytokine expression, and fibrosis was evaluated by Masson staining and measuring fibrotic biomarker expression. Results: We found that LMK235 ameliorated cardiac dysfunction post-MI by suppressing inflammation and fibrosis, and LMK235 inhibited upregulation of lysine-specific demethylase 1 (LSD1) expression post-MI. In macrophages, LMK235 attenuated lipopolysaccharide (LPS) - induced inflammatory cytokine expression and inhibited LSD1 expression, while overexpression of LSD1 abrogated the anti-inflammatory effect of LMK235. In cardiac fibroblasts, LMK235 attenuated transforming growth factor-beta 1 (TGF-beta 1) - induced fibrotic biomarker expression and inhibited LSD1 expression, while overexpression of LSD1 abrogated the antifibrotic effect of LMK235. Conclusion: LMK235 attenuates chronic inflammation and fibrosis post-MI, leading to improved cardiac function. The anti-inflammatory effect of LMK235 may result from inhibition of the LSD1-NF-kappa B pathway in macrophages. The antifibrotic effect of LMK235 may result from inhibition of the LSD1-Smad2/3 pathway in cardiac fibroblasts.
资助项目	The Natural Science Foundation of Zhejiang Province [LY19H020006]
出版者	NATURE PORTFOLIO
ISSN	2045-2322
卷号	14 期号:1
DOI	10.1038/s41598-024-74887-3
页数	13
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:001331683000089
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39379699
SCOPUSEID	2-s2.0-85206038431
通讯作者地址	[Li, Lei;Lin, Jiafeng]Wenzhou Med Univ, Affiliated Hosp 2, Dept Cardiol, Yuying Childrens Hosp, Wenzhou, Zhejiang, Peoples R China.
Scopus学科分类	Multidisciplinary
SCOPUS_ID	SCOPUS_ID:85206038431
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/220808
专题	附属第一医院_超声影像科附属第二医院附属第二医院_耳鼻咽喉科附属第一医院第二临床医学院、附属第二医院、育英儿童医院
通讯作者	Li, Lei; Lin, Jiafeng
作者单位	1.Wenzhou Med Univ, Dept Ultrasonog, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 2, Dept Cardiol, Yuying Childrens Hosp, Wenzhou, Zhejiang, Peoples R China
第一作者单位	超声影像科; 附属第一医院; 附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 耳鼻咽喉科
通讯作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 耳鼻咽喉科
第一作者的第一单位	超声影像科
推荐引用方式 GB/T 7714	Lv, Fangzhou,Xie, Laidi,Li, Lei,et al. LMK235 ameliorates inflammation and fibrosis after myocardial infarction by inhibiting LSD1-related pathway[J]. Scientific Reports,2024,14(1).
APA	Lv, Fangzhou, Xie, Laidi, Li, Lei, & Lin, Jiafeng. (2024). LMK235 ameliorates inflammation and fibrosis after myocardial infarction by inhibiting LSD1-related pathway. Scientific Reports, 14(1).
MLA	Lv, Fangzhou,et al."LMK235 ameliorates inflammation and fibrosis after myocardial infarction by inhibiting LSD1-related pathway".Scientific Reports 14.1(2024).