MafB promotes atherosclerosis by inhibiting foam-cell apoptosis.

Abstract

MafB is a transcription factor that induces myelomonocytic differentiation. However, the precise role of MafB in the pathogenic function of macrophages has never been clarified. Here we demonstrate that MafB promotes hyperlipidemic atherosclerosis by suppressing foam-cell apoptosis. Our data show that MafB is predominantly expressed in foam cells found within atherosclerotic lesions, where MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM). In the absence of MafB, activated LXR/RXR fails to induce the expression of AIM, a protein that is normally responsible for protecting macrophages from apoptosis; thus, Mafb-deficient macrophages are prone to apoptosis. Haematopoietic reconstitution with Mafb-deficient fetal liver cells in recipient LDL receptor-deficient hyperlipidemic mice revealed accelerated foam-cell apoptosis, which subsequently led to the attenuation of the early atherogenic lesion. These findings represent the first evidence that the macrophage-affiliated MafB transcription factor participates in the acceleration of atherogenesis.

• Authors: Michito Hamada, Megumi Nakamura, Mai Thi Nhu Tran, Takashi Moriguchi, Cynthia Hong, Takayuki Ohsumi, Tra Thi Huong Dinh, Manabu Kusakabe, Motochika Hattori, Tokio Katsumata, Satoko Arai, Katsuhiko Nakashima, Takashi Kudo, Etsushi Kuroda, Chien-Hui Wu, Pei-Han Kao, Masaharu Sakai, Hitoshi Shimano, Toru Miyazaki, Peter Tontonoz, Satoru Takahashi
• Journal: Nature communications (Nat Commun) Vol. 5 Pg. 3147 ( 2014) ISSN: 2041-1723 [Electronic] England
• PMID: 24445679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• Cd5l protein, mouse
• Liver X Receptors
• MafB Transcription Factor
• Mafb protein, mouse
• Orphan Nuclear Receptors
• Receptors, Immunologic
• Receptors, Scavenger
• Retinoid X Receptors

Topics

• Animals
• Apoptosis
• Apoptosis Regulatory Proteins (genetics)
• Atherosclerosis (pathology, physiopathology)
• Base Sequence
• Foam Cells (pathology)
• Humans
• Liver X Receptors
• MafB Transcription Factor (genetics, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Molecular Sequence Data
• Orphan Nuclear Receptors (metabolism)
• Receptors, Immunologic (genetics)
• Receptors, Scavenger
• Retinoid X Receptors (metabolism)
• Sequence Homology, Nucleic Acid