KLF15 regulates macrophage polarization patterns in deep vein thrombosis

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Biology

Background:

• Krüppel-like factor 15 (KLF15) is implicated in cardiovascular diseases, influencing vascular remodeling and metabolic functions.
• Macrophages play a critical role in deep vein thrombosis (DVT) by mediating inflammation and modulating the fibrinolytic system.

Purpose of the Study:

• To investigate the role of KLF15 in macrophage polarization within the context of DVT.
• To elucidate the molecular mechanisms by which KLF15 affects macrophage phenotypes in DVT.

Main Methods:

• Establishment of a DVT animal model to analyze KLF15 expression and macrophage polarization in vivo.
• In vitro studies using PMA-treated THP-1 cells with KLF15 overexpression to induce M1 and M2-like macrophage polarization, followed by molecular and cellular assays.
• Chromatin accessibility assays (CUT&Tag) and Chromatin immunoprecipitation (ChIP) to identify KLF15 binding sites and downstream targets.

Main Results:

• In vivo, DVT models showed elevated levels of KLF15 and inflammatory markers (iNOS, IL-1β, IL-6) alongside altered macrophage markers (CD206, IL-10, TGF-β).
• In vitro, KLF15 overexpression enhanced M1-like macrophage polarization, increasing pro-inflammatory mediators (iNOS, CD86, IL-12, TNF-α, IL-1β, IL-6) and decreasing M2 markers (CD206, IL-10, ARG1, TGF-β).
• KLF15 was found to bind the NEK2 promoter in M1-like macrophages, promoting its transcription and activating the NF-κB pathway.

Conclusions:

• KLF15 actively promotes M1 macrophage polarization in DVT, primarily through the NEK2/NF-κB signaling axis.
• KLF15 emerges as a promising therapeutic target for DVT management.
• Further research is necessary to explore the clinical applicability and detailed mechanistic aspects of KLF15 in DVT.