Tags

Type your tag names separated by a space and hit enter

Tumor necrosis factor-alpha promotes atherosclerotic lesion progression in APOE*3-Leiden transgenic mice.
Cardiovasc Res. 2005 Apr 01; 66(1):179-85.CR

Abstract

OBJECTIVE

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.

METHODS AND RESULTS

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).

CONCLUSIONS

Our data indicate that TNFalpha stimulates the formation of lesions towards an advanced phenotype, with more lesion necrosis and a lower incidence of apoptosis.

Authors+Show Affiliations

Department of General Internal Medicine, Leiden University Medical Center, The Netherlands. lsm.boesten@pg.tno.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15769461

Citation

Boesten, Lianne S M., et al. "Tumor Necrosis Factor-alpha Promotes Atherosclerotic Lesion Progression in APOE*3-Leiden Transgenic Mice." Cardiovascular Research, vol. 66, no. 1, 2005, pp. 179-85.
Boesten LS, Zadelaar AS, van Nieuwkoop A, et al. Tumor necrosis factor-alpha promotes atherosclerotic lesion progression in APOE*3-Leiden transgenic mice. Cardiovasc Res. 2005;66(1):179-85.
Boesten, L. S., Zadelaar, A. S., van Nieuwkoop, A., Gijbels, M. J., de Winther, M. P., Havekes, L. M., & van Vlijmen, B. J. (2005). Tumor necrosis factor-alpha promotes atherosclerotic lesion progression in APOE*3-Leiden transgenic mice. Cardiovascular Research, 66(1), 179-85.
Boesten LS, et al. Tumor Necrosis Factor-alpha Promotes Atherosclerotic Lesion Progression in APOE*3-Leiden Transgenic Mice. Cardiovasc Res. 2005 Apr 1;66(1):179-85. PubMed PMID: 15769461.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2005/01/28/ PY - 2004/11/03/received PY - 2004/12/24/revised PY - 2005/01/03/accepted PY - 2005/3/17/pubmed PY - 2005/8/6/medline PY - 2005/3/17/entrez SP - 179 EP - 85 JF - Cardiovascular research JO - Cardiovasc Res VL - 66 IS - 1 N2 - OBJECTIVE: 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. METHODS AND RESULTS: 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). CONCLUSIONS: Our data indicate that TNFalpha stimulates the formation of lesions towards an advanced phenotype, with more lesion necrosis and a lower incidence of apoptosis. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/15769461/Tumor_necrosis_factor_alpha_promotes_atherosclerotic_lesion_progression_in_APOE_3_Leiden_transgenic_mice_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1016/j.cardiores.2005.01.001 DB - PRIME DP - Unbound Medicine ER -