Abstract
Inflammatory cytokines, including tumor necrosis factor-α (TNF-α) have been implicated in atherogenesis. However, the precise role of TNF-α in atherogenesis is still unclear. To examine the effect of TNF-α on atherogenesis, we generated compound-deficient mice in apolipoprotein E (apoE) and TNF-α (apoE-/-/TNF-α -/-) and compared them with apoE-/- mice. Although serum total cholesterol levels were markedly elevated in both apoE-/-/TNF- α-/- and apoE-/- mice compared to wild-type mice, no differences were observed between apoE-/-/TNF-α-/- and apoE-/- mice. The atherosclerotic plaque area in the aortic luminal surface of apoE-/-/TNF-α-/- mice (n = 8, 3.1 ± 0.4%) was significantly smaller than that of apoE-/- mice (n = 7, 4.7 ± 0.4%, p < 0.001) despite the lack of difference in serum cholesterol levels. The atherosclerotic lesion size in the aortic sinus of apoE-/-/TNF-α-/- mice (n = 10, 5.1 ± 0.3 × l05 μm2) was also significantly smaller than that of apoE-/- mice (n = 11, 7.0 ± 0.3 × l05 μm2, p < 0.0001). RT-PCR analysis indicated that the expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in apoE-/- than apoE-/-/TNF- α-/- mice. Macrophages from apoE-/- mice showed higher uptake level of oxidized LDL and increased expression level of scavenger receptor class A (SRA) compared to those from apoE-/-/TNF- α-/- mice. These results indicate that TNF-α plays an atherogenic role by upregulating the expressions of ICAM-1, VCAM-1 and MCP-1 in the vascular wall, and by inducing SRA expression and oxidized LDL uptake in macrophages.
| Original language | English |
|---|---|
| Pages (from-to) | 11-17 |
| Number of pages | 7 |
| Journal | Atherosclerosis |
| Volume | 180 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 01-01-2005 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
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Disruption of tumor necrosis factor-α gene diminishes the development of atherosclerosis in ApoE-deficient mice. / Ohta, Hirotoshi; Wada, Hisayasu; Niwa, Tamikazu; Kirii, Hirokazu; Iwamoto, Naoki; Fujii, Hidehiko; Saito, Kuniaki; Sekikawa, Kenji; Seishima, Mitsuru.
In: Atherosclerosis, Vol. 180, No. 1, 01.01.2005, p. 11-17.Research output: Contribution to journal › Article
TY - JOUR
T1 - Disruption of tumor necrosis factor-α gene diminishes the development of atherosclerosis in ApoE-deficient mice
AU - Ohta, Hirotoshi
AU - Wada, Hisayasu
AU - Niwa, Tamikazu
AU - Kirii, Hirokazu
AU - Iwamoto, Naoki
AU - Fujii, Hidehiko
AU - Saito, Kuniaki
AU - Sekikawa, Kenji
AU - Seishima, Mitsuru
PY - 2005/1/1
Y1 - 2005/1/1
N2 - Inflammatory cytokines, including tumor necrosis factor-α (TNF-α) have been implicated in atherogenesis. However, the precise role of TNF-α in atherogenesis is still unclear. To examine the effect of TNF-α on atherogenesis, we generated compound-deficient mice in apolipoprotein E (apoE) and TNF-α (apoE-/-/TNF-α -/-) and compared them with apoE-/- mice. Although serum total cholesterol levels were markedly elevated in both apoE-/-/TNF- α-/- and apoE-/- mice compared to wild-type mice, no differences were observed between apoE-/-/TNF-α-/- and apoE-/- mice. The atherosclerotic plaque area in the aortic luminal surface of apoE-/-/TNF-α-/- mice (n = 8, 3.1 ± 0.4%) was significantly smaller than that of apoE-/- mice (n = 7, 4.7 ± 0.4%, p < 0.001) despite the lack of difference in serum cholesterol levels. The atherosclerotic lesion size in the aortic sinus of apoE-/-/TNF-α-/- mice (n = 10, 5.1 ± 0.3 × l05 μm2) was also significantly smaller than that of apoE-/- mice (n = 11, 7.0 ± 0.3 × l05 μm2, p < 0.0001). RT-PCR analysis indicated that the expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in apoE-/- than apoE-/-/TNF- α-/- mice. Macrophages from apoE-/- mice showed higher uptake level of oxidized LDL and increased expression level of scavenger receptor class A (SRA) compared to those from apoE-/-/TNF- α-/- mice. These results indicate that TNF-α plays an atherogenic role by upregulating the expressions of ICAM-1, VCAM-1 and MCP-1 in the vascular wall, and by inducing SRA expression and oxidized LDL uptake in macrophages.
AB - Inflammatory cytokines, including tumor necrosis factor-α (TNF-α) have been implicated in atherogenesis. However, the precise role of TNF-α in atherogenesis is still unclear. To examine the effect of TNF-α on atherogenesis, we generated compound-deficient mice in apolipoprotein E (apoE) and TNF-α (apoE-/-/TNF-α -/-) and compared them with apoE-/- mice. Although serum total cholesterol levels were markedly elevated in both apoE-/-/TNF- α-/- and apoE-/- mice compared to wild-type mice, no differences were observed between apoE-/-/TNF-α-/- and apoE-/- mice. The atherosclerotic plaque area in the aortic luminal surface of apoE-/-/TNF-α-/- mice (n = 8, 3.1 ± 0.4%) was significantly smaller than that of apoE-/- mice (n = 7, 4.7 ± 0.4%, p < 0.001) despite the lack of difference in serum cholesterol levels. The atherosclerotic lesion size in the aortic sinus of apoE-/-/TNF-α-/- mice (n = 10, 5.1 ± 0.3 × l05 μm2) was also significantly smaller than that of apoE-/- mice (n = 11, 7.0 ± 0.3 × l05 μm2, p < 0.0001). RT-PCR analysis indicated that the expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in apoE-/- than apoE-/-/TNF- α-/- mice. Macrophages from apoE-/- mice showed higher uptake level of oxidized LDL and increased expression level of scavenger receptor class A (SRA) compared to those from apoE-/-/TNF- α-/- mice. These results indicate that TNF-α plays an atherogenic role by upregulating the expressions of ICAM-1, VCAM-1 and MCP-1 in the vascular wall, and by inducing SRA expression and oxidized LDL uptake in macrophages.
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U2 - 10.1016/j.atherosclerosis.2004.11.016
DO - 10.1016/j.atherosclerosis.2004.11.016
M3 - Article
VL - 180
SP - 11
EP - 17
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 1
ER -