TY - JOUR
T1 - Thalidomide inhibits early atherogenesis in apoE-deficient mice
AU - Chew, Michelle
AU - Zhou, Ji
AU - Daugherty, Alan
AU - Eriksson, Tommy
AU - Ellermann-Eriksen, Svend
AU - Hansen, Peter Riis
AU - Falk, Erling
PY - 2003
Y1 - 2003
N2 - Inflammation is present in all stages of atherosclerosis, from fatty streaks to rupture of mature plaques. Tumour necrosis factor (TNF)-α is expressed in atherosclerotic lesions but its role in atherogenesis has not been defined. To clarify the role of this cytokine, we administered thalidomide, a compound known to inhibit TNF-α production, to homozygous apolipoprotein E-deficient (apoE-/-) mice in order to examine the effect of thalidomide on the development of early atherosclerotic lesions. Twelve apoE-/- mice were randomized to receive either sustained-release thalidomide or placebo pellets implanted subcutaneously, and the amount of atherosclerosis was quantified six weeks later. Thalidomide was well tolerated and did not result in any changes in body weight. Mice treated with thalidomide had significantly smaller mean (79865±5189 vs 19607±10353 μm2, p=0.05) and maximum (15800 [12777-23675] vs 37169 [28000-41351] μm2, p=0.03) lesion sizes than those treated with placebo. Thus, thalidomide is capable of inhibiting the early development of atherosclerosis, presumably by inhibition of TNF-α secretion.
AB - Inflammation is present in all stages of atherosclerosis, from fatty streaks to rupture of mature plaques. Tumour necrosis factor (TNF)-α is expressed in atherosclerotic lesions but its role in atherogenesis has not been defined. To clarify the role of this cytokine, we administered thalidomide, a compound known to inhibit TNF-α production, to homozygous apolipoprotein E-deficient (apoE-/-) mice in order to examine the effect of thalidomide on the development of early atherosclerotic lesions. Twelve apoE-/- mice were randomized to receive either sustained-release thalidomide or placebo pellets implanted subcutaneously, and the amount of atherosclerosis was quantified six weeks later. Thalidomide was well tolerated and did not result in any changes in body weight. Mice treated with thalidomide had significantly smaller mean (79865±5189 vs 19607±10353 μm2, p=0.05) and maximum (15800 [12777-23675] vs 37169 [28000-41351] μm2, p=0.03) lesion sizes than those treated with placebo. Thus, thalidomide is capable of inhibiting the early development of atherosclerosis, presumably by inhibition of TNF-α secretion.
KW - Atherosclerosis
KW - Cytokines
KW - Inflammation
KW - Pathology
KW - TNF-α
KW - Thalidomide
UR - http://www.scopus.com/inward/record.url?scp=0037663818&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037663818&partnerID=8YFLogxK
M3 - Article
C2 - 12874961
AN - SCOPUS:0037663818
SN - 0903-465X
VL - 111
SP - 113
EP - 116
JO - APMIS, Supplement
JF - APMIS, Supplement
IS - 109
ER -