AIM: Increased levels of small dense low-density lipoproteins (sd-LDL) have been reported more atherogenic compared to total low-density lipoprotein (LDL); however, no definitive experiments using macrophages have examined this concept in vitro. METHOD AND RESULT: In this study, we isolated fractions of total LDL (density 1.019-1.063 g/ml) and sd-LDL (density 1.044-1.063 g/ml) from the plasma of subjects with modest hypertriglycidemia. Oxidizabilty as assessed by copper-induced generation (1.6 µmol/L CuSO(4),12 h) of thiobarbituric acid reactive substances (TBARS) was significantly greater (7-fold higher, p < 0.01) for sd-LDL (4.3 ± 1.1 nmol/mg) than for total LDL (0.6 ± 0.2 nmol/mg) at the same cholesterol concentrations. Moreover, oxidized sd-LDL induced more lipid staining in macrophages than oxidized total LDL. When non-oxidized sd-LDL were incubated with THP1 macrophages, there was much greater lipid accumulation as assessed by oil red O staining, and more than a 2-fold increase (p < 0.05) in intracellular triglyceride content as compared to non-oxidized total LDL. Furthermore, non-oxidized sd-LDL in contrast to non-oxidized total LDL enhanced macrophage lectin-like oxidized LDL receptor-1 (LOX-1) protein expression and significantly LOX-1 mRNA levels (+158%, p < 0.05), with no effect on scavenger receptor A or CD36 gene expression. These effects of non-oxidized sd-LDL on LOX-1 gene expression were suppressed when Toll-like receptor 4 was inactivated either by RNAi or antibody. CONCLUSION: Our data indicate for the first time that sd-LDL is much more effective in promoting macrophage triglyceride accumulation and LOX-1 gene expression than total LDL.
AIM: Increased levels of small dense low-density lipoproteins (sd-LDL) have been reported more atherogenic compared to total low-density lipoprotein (LDL); however, no definitive experiments using macrophages have examined this concept in vitro. METHOD AND RESULT: In this study, we isolated fractions of total LDL (density 1.019-1.063 g/ml) and sd-LDL (density 1.044-1.063 g/ml) from the plasma of subjects with modest hypertriglycidemia. Oxidizabilty as assessed by copper-induced generation (1.6 µmol/L CuSO(4),12 h) of thiobarbituric acid reactive substances (TBARS) was significantly greater (7-fold higher, p < 0.01) for sd-LDL (4.3 ± 1.1 nmol/mg) than for total LDL (0.6 ± 0.2 nmol/mg) at the same cholesterol concentrations. Moreover, oxidized sd-LDL induced more lipid staining in macrophages than oxidized total LDL. When non-oxidized sd-LDL were incubated with THP1 macrophages, there was much greater lipid accumulation as assessed by oil red O staining, and more than a 2-fold increase (p < 0.05) in intracellular triglyceride content as compared to non-oxidized total LDL. Furthermore, non-oxidized sd-LDL in contrast to non-oxidized total LDL enhanced macrophage lectin-like oxidized LDL receptor-1 (LOX-1) protein expression and significantly LOX-1 mRNA levels (+158%, p < 0.05), with no effect on scavenger receptor A or CD36 gene expression. These effects of non-oxidized sd-LDL on LOX-1 gene expression were suppressed when Toll-like receptor 4 was inactivated either by RNAi or antibody. CONCLUSION: Our data indicate for the first time that sd-LDL is much more effective in promoting macrophage triglyceride accumulation and LOX-1 gene expression than total LDL.
Authors: Núria Puig; Lara Montolio; Pol Camps-Renom; Laia Navarra; Francesc Jiménez-Altayó; Elena Jiménez-Xarrié; Jose Luis Sánchez-Quesada; Sonia Benitez Journal: Cells Date: 2020-03-01 Impact factor: 6.600
Authors: Maria Pia Adorni; Marta Biolo; Francesca Zimetti; Marcella Palumbo; Nicoletta Ronda; Paolo Scarinzi; Paolo Simioni; Maria Giovanna Lupo; Nicola Ferri; Lorenzo Previato; Franco Bernini; Alberto Zambon Journal: Int J Mol Sci Date: 2022-07-26 Impact factor: 6.208