TY - JOUR
T1 - Tumor necrosis factor-alpha promotes atherosclerotic lesion progression in APOE*3-Leiden transgenic mice
AU - Boesten, Lianne S. M.
AU - Zadelaar, A. Susanne M.
AU - van Nieuwkoop, Anita
AU - Gijbels, Marion J. J.
AU - de Winther, Menno P. J.
AU - Havekes, Louis M.
AU - van Vlijmen, Bart J. M.
PY - 2005
Y1 - 2005
N2 - Tumor necrosis factor-alpha (TNFalpha) is a pleiotropic cytokine exerting both inflammatory and cell death modulatory activity, and is thought to play a role in the pathogenesis of atherosclerosis. Studies in mice indicated that TNFalpha affects atherosclerosis minimally or not under conditions that allow fatty streak formation. Here, we examined the possible role of TNFalpha in advanced and complex atherosclerotic lesions. To induce atherosclerosis, TNFalpha-deficient (Tnf-/-) APOE*3-Leiden and control APOE*3-Leiden only mice were fed a cholesterol-rich diet. Comparable levels of plasma cholesterol and triglycerides and the systemic inflammatory parameters, serum amyloid A and soluble intercellular adhesion molecule-1 were found in APOE*3-LeidenTnf-/- and control mice. Although absence of TNFalpha did not affect the quantitative area of atherosclerosis, APOE*3-LeidenTnf-/- mice had a higher relative number of early lesions (46.1% vs. 21.4%) and a lower relative number of advanced lesions (53.9% vs. 78.6%, P=0.04). In addition, the advanced lesions in APOE*3-LeidenTnf-/- mice showed less necrosis (9.9+/-12.1% vs. 23.4+/-19.3% of total lesion area, P=0.04) and an increase in apoptosis (1.5+/-1.5% vs. 0.4+/-0.6% of total nuclei, P=0.03). Our data indicate that TNFalpha stimulates the formation of lesions towards an advanced phenotype, with more lesion necrosis and a lower incidence of apoptosis
AB - Tumor necrosis factor-alpha (TNFalpha) is a pleiotropic cytokine exerting both inflammatory and cell death modulatory activity, and is thought to play a role in the pathogenesis of atherosclerosis. Studies in mice indicated that TNFalpha affects atherosclerosis minimally or not under conditions that allow fatty streak formation. Here, we examined the possible role of TNFalpha in advanced and complex atherosclerotic lesions. To induce atherosclerosis, TNFalpha-deficient (Tnf-/-) APOE*3-Leiden and control APOE*3-Leiden only mice were fed a cholesterol-rich diet. Comparable levels of plasma cholesterol and triglycerides and the systemic inflammatory parameters, serum amyloid A and soluble intercellular adhesion molecule-1 were found in APOE*3-LeidenTnf-/- and control mice. Although absence of TNFalpha did not affect the quantitative area of atherosclerosis, APOE*3-LeidenTnf-/- mice had a higher relative number of early lesions (46.1% vs. 21.4%) and a lower relative number of advanced lesions (53.9% vs. 78.6%, P=0.04). In addition, the advanced lesions in APOE*3-LeidenTnf-/- mice showed less necrosis (9.9+/-12.1% vs. 23.4+/-19.3% of total lesion area, P=0.04) and an increase in apoptosis (1.5+/-1.5% vs. 0.4+/-0.6% of total nuclei, P=0.03). Our data indicate that TNFalpha stimulates the formation of lesions towards an advanced phenotype, with more lesion necrosis and a lower incidence of apoptosis
U2 - https://doi.org/10.1016/j.cardiores.2005.01.001
DO - https://doi.org/10.1016/j.cardiores.2005.01.001
M3 - Article
C2 - 15769461
SN - 0008-6363
VL - 66
SP - 179
EP - 185
JO - Cardiovascular research
JF - Cardiovascular research
IS - 1
ER -