FABP5 Is a Sensitive Marker for Lipid-Rich Macrophages in the Luminal Side of Atherosclerotic Lesions
Yogi Umbarawan, Aiko Enoura, Harumi Ogura, Tomohito Sato, Makoto Horikawa, Tomoaki Ishii, Hiroaki Sunaga, Hiroki Matsui, Tomoyuki Yokoyama, Ryo Kawakami, Toshitaka Maeno, Mitsutoshi Setou, Masahiko Kurabayashi, Tatsuya Iso
Abstract
Lipid-rich macrophages in atherosclerotic lesions are thought to be derived from myeloid and vascular smooth muscle cells. A series of studies with genetic and pharmacological inhibition of fatty acid binding protein 4 (FABP4) and FABP5 and bone marrow transplant experiments with FABP4/5 deficient cells in mice have demonstrated that these play an important role in the development of atherosclerosis. However, it is still uncertain about the differential cell-type specificity and distribution between FABP4- and FABP5-expressing cells in early- and late-stage atherosclerotic lesions. In this study, we first explored spatial distribution of FABP4/5 in atherosclerotic lesions in apolipoprotein E deficient (ApoE-/-) mice. FABP4 was only marginally detected in early and advanced lesions, whereas FABP5 was abundantly expressed in these lesions. In advanced lesions, the FABP5-positive area was mostly restricted to the foam cell layer adjacent to the lumen above collagen and elastic fibers with a high signal/noise ratio. Oil red O (ORO) staining revealed that FABP5-positive cells were lipid-rich in early and advanced lesions. Together, most of lipid-rich FABP5-positive cells reside adjacent to the lumen above collagen and elastic fibers. We next studied involvement of FABP5 in lesion formation of atherosclerosis using ApoE-/- FABP5-/- mice. However, deletion of FABP5 did not affect the development of atherosclerosis. These findings, along with previous reports, suggest a novel notion that FABP5 is a sensitive marker for bone marrow-derived lipid-rich macrophages in the luminal side of atherosclerotic lesions, although its functional significance remains elusive.