The macrophage-derived motor protein KIF13B enhances MERTK-mediated efferocytosis and prevents atherosclerosis in mice
Authors' conclusion
The study results revealed that KIF13B is a crucial modulator responsible for maintaining proper macrophage efferocytosis to prevent atherosclerotic development through KIF13B/ITCH/CBL/MERTK axis
Study context
- Population
- Mice fed a Western diet for 12 weeks; patients with atherosclerosis (carotid plaques)
- Comparison
- Kif13b deficiency vs control
Methodological detailsmouse models, human cohort data and carotid plaques, bone marrow transplantation, in vitro macrophage studies
- Mouse models
- Human cohort data and carotid plaques
- Bone marrow transplantation
- In vitro macrophage studies
Main finding
As reported in the abstract
- KIF13B expression significantly reduced in patients with atherosclerosis and negatively associated with atherosclerosis severity in Western diet (WD)-fed low-density lipoprotein receptor (Ldlr)-/- mice
- Kif13b-/-;Ldlr-/- mice: significantly increased plasma total cholesterol and more atherosclerotic lesions vs controls
- Myeloid Kif13b depletion and bone marrow transplantation with Kif13b-deficient macrophages: plasma lipids unchanged but larger plaques with more macrophage infiltration and more apoptotic cells
- Kif13b-deficient macrophages (oxidized LDL): significantly increased cholesterol accumulation and impaired efferocytosis with reduced MERTK expression
- Loss of Kif13b decreased ITCH expression, accelerating CBL-mediated ubiquitination and degradation of MERTK
- Oral NX-1607 (CBL antagonist) significantly reversed reduced MERTK and defective efferocytosis and protected against atherosclerosis caused by Kif13b deficiency in vivo
Original publication
The macrophage-derived motor protein KIF13B enhances MERTK-mediated efferocytosis and prevents atherosclerosis in mice. Eur Heart J. Published 25 July 2025. doi:10.
Summarised from the published abstract; every number is checked against it