Role of macrophage scavenger receptors in diet-induced atherosclerosis in mice

Hisashi Sakaguchi, Motohiro Takeya, Hiroshi Suzuki, Hideki Hakamata, Tatsuhiko Kodama, Seikoh Horiuchi, Siamon Gordon, Luc J.W. Van Der Laan, Georg Kraal, Shun Ishibashi, Nobuo Kitamura, Kiyoshi Takahashi*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

128 Citations (Scopus)

Abstract

To clarify the role of type I and type II macrophage scavenger receptors (MSR-A) in the progression of diet-induced atherosclerosis, we generated mice lacking both MSR-A and low-density lipoprotein receptor (LDLR). After 4 or 12 weeks of a high-fat diet, the sizes of atherosclerotic lesions in MSR-A/LDLR double knockout mice were significantly reduced (p < 0.05) compared with those in LDLR single knockout mice. However, atherosclerotic lesions mainly composed of foamy macrophages were still observed in double knockout mice. Formation of atherosclerotic lesions in double knockout mice was partially explained by the participation of scavenger receptors other than MSR-A such as MARCO, CD36, and macrosialin/CD68. These receptors were clearly demonstrated in the atherosclerotic lesions in double knockout mice as well as LDLR single knockout mice by immunohistochemistry or by reverse transcriptase-polymerase chain reaction. Because the very low density lipoprotein (VLDL) fraction was elevated in the double and single knockout mice, we further examined the possibility that VLDL may participate in foam cell formation in atherosclerotic lesions. When incubated with VLDL isolated from LDLR-deficient mice, cholesterol ester accumulation and foamy transformation occurred in MSR-A-deficient macrophages as well as in normal macrophages. These data indicate that MSR-A plays an essential role in the development of diet-induced atherosclerosis. It also appears that other scavenger receptors, such as MARCO, CD36, and macrosialin/CD68, as well as uptake of VLDL are involved in foam cell formation during atherogenesis in MSR-A/LDLR double knockout mice.

Original languageEnglish
Pages (from-to)423-434
Number of pages12
JournalLaboratory Investigation
Volume78
Issue number4
Publication statusPublished - Apr 1998
Externally publishedYes

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