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.
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: Pedro Melgar-Lesmes; Fernando Garcia-Polite; Paula Del-Rey-Puech; Elisabet Rosas; Juliana L Dreyfuss; Eulàlia Montell; Josep Vergés; Elazer R Edelman; Mercedes Balcells Journal: Atherosclerosis Date: 2015-12-13 Impact factor: 5.162
Authors: Divay Chandra; James Londino; Shaun Alexander; Joseph S Bednash; Yingze Zhang; Robert M Friedlander; Grant Daskivich; Diane L Carlisle; William R Lariviere; Ana Carolina Igami Nakassa; Mark Ross; Claudette St Croix; Toru Nyunoya; Frank Sciurba; Bill Chen; Rama K Mallampalli Journal: J Mol Cell Cardiol Date: 2018-11-16 Impact factor: 5.000
Authors: Brittany G Durgin; Olga A Cherepanova; Delphine Gomez; Themistoclis Karaoli; Gabriel F Alencar; Joshua T Butcher; Yu-Qing Zhou; Michelle P Bendeck; Brant E Isakson; Gary K Owens; Jessica J Connelly Journal: Am J Physiol Heart Circ Physiol Date: 2017-03-10 Impact factor: 4.733
Authors: Pedro Melgar-Lesmes; Alvaro Sánchez-Herrero; Ferran Lozano-Juan; Jose María de la Torre Hernández; Eulàlia Montell; Wladimiro Jiménez; Elazer R Edelman; Mercedes Balcells Journal: Thromb Haemost Date: 2018-06-06 Impact factor: 5.249