Dietary cholesterol plays a role in CD36-mediated atherogenesis in LDLR-knockout mice.
OBJECTIVE
CD36 has been shown to play a role in atherosclerosis in the apolipoprotein E-knockout (apoE(o)) mouse. We observed no difference in aortic lesion area between Western diet (WD)-fed LDLR(o) and LDLR(o)/CD36(o) mice. The objective was to understand the mechanism of CD36-dependent atherogenesis.


RESULTS
ApoE(o) mice transplanted with bone marrow from LDLR(o)/CD36(o) mice had significantly less aortic lesion compared with those transplanted with LDLR(o) marrow. Reciprocal macrophage transfer into hyperlipidemic apoE(o) and LDLR(o) animals showed that foam cell formation induced by in vivo modified lipoproteins was dependent on the lipoprotein, not macrophage type. LDLR(o) and LDLR(o)/CD36(o) mice were fed a cholesterol-enriched diet (HC), and we observed significant lesion inhibition in LDLR(o)/CD36(o) mice. LDL/plasma isolated from HC-fed LDLR(o) mice induced significantly greater jnk phosphorylation, cytokine release, and reactive oxygen species secretion than LDL/plasma from WD-fed LDLR(o) mice, and this was CD36-dependent. HC-fed LDLR(o) mice had higher circulating levels of cytokines than WD-fed mice.


CONCLUSIONS
These data support the hypothesis that CD36-dependent atherogenesis is contingent on a proinflammatory milieu that promotes the creation of specific CD36 ligands, not solely hypercholesterolemia, and may explain the greater degree/accelerated rate of atherosclerosis observed in syndromes associated with inflammatory risk.
Kennedy
David J
DJ
Department of Cell Biology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Kuchibhotla
Sai D
SD
Guy
Ella
E
Park
Young Mi
YM
Nimako
George
G
Vanegas
DiFernando
D
Morton
Richard E
RE
Febbraio
Maria
M
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology*; D018955:CD36 Antigens / Q000502:physiology*; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000502:physiology*
D001057:Apolipoproteins E; D018955:CD36 Antigens; D002791:Cholesterol, Dietary; D016207:Cytokines; D011973:Receptors, LDL