KLF9 deficiency protects the heart from inflammatory injury triggered by myocardial infarction
1Department of Cardiology, Heji Hospital of Changzhi Medical College, Changzhi 046011, China.
Insights
Kruppel-like factor 9 (KLF9) promotes inflammation after heart attack by activating macrophages. Targeting KLF9 may offer a new treatment for ischemic heart disease, improving cardiac function and reducing heart failure risk.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Immunology
Background:
- Myocardial infarction triggers inflammation, worsening heart injury and leading to heart failure.
- Transcription factors regulate cardiovascular disease, but KLF9's role in myocardial infarction-induced inflammation is unknown.
Purpose of the Study:
- To investigate the role of KLF9 in myocardial infarction-induced inflammation and its potential as a therapeutic target.
Main Methods:
- Examined KLF9 expression in myocardial infarction models.
- Assessed the impact of KLF9 deficiency on cardiac function and remodeling.
- Investigated KLF9's effects on macrophage inflammatory responses, NF-κB, MAPK, and TLR2 signaling.
Main Results:
- KLF9 expression increased during myocardial infarction, particularly in macrophages.
- KLF9 deficiency improved cardiac function and reduced adverse remodeling.
- KLF9 downregulation suppressed macrophage inflammation by inhibiting NF-κB and MAPK signaling.
- KLF9 directly binds the TLR2 promoter, enhancing its expression and promoting inflammation.
Conclusions:
- KLF9 acts as a pro-inflammatory transcription factor in macrophages post-myocardial infarction.
- Targeting KLF9 presents a potential therapeutic strategy for ischemic heart disease.
Abstract:
The excessive inflammatory response induced by myocardial infarction exacerbates heart injury and leads to the development of heart failure. Recent studies have confirmed the involvement of multiple transcription factors in the modulation of cardiovascular disease processes. However, the role of KLF9 in the inflammatory response induced by cardiovascular diseases including myocardial infarction remains unclear. Here, we found that the expression of KLF9 significantly increased during myocardial infarction. Besides, we also detected high expression of KLF9 in infiltrated macrophages after myocardial infarction. Our functional studies revealed that KLF9 deficiency prevented cardiac function and adverse cardiac remodeling. Furthermore, the downregulation of KLF9 inhibited the activation of NF-κB and MAPK signaling, leading to the suppression of inflammatory responses of macrophages triggered by myocardial infarction. Mechanistically, KLF9 was directly bound to the TLR2 promoter to enhance its expression, subsequently promoting the activation of inflammation-related signaling pathways. Our results suggested that KLF9 is a pro-inflammatory transcription factor in macrophages and targeting KLF9 may be a novel therapeutic strategy for ischemic heart disease.
Related Concept Videos
01:21Myocarditis I: Introduction
01:17Ischemic Heart Disease: Overview
Atherosclerosis, the primary malefactor, orchestrates this dangerous condition. It manifests as the accumulation of fatty deposits, akin to insidious plaques, within arterial walls. As time elapses, these plaques metamorphose, hardening and...