Atorvastatin decreases lipoprotein lipase and endothelial lipase expression in human THP-1 macrophages

Macrophage-derived lipases are associated with atherosclerosis in human and animal studies. Despite numerous non-lipid-lowering effects of statins, their effect on macrophage LPL and endothelial lipase (EL) expression has not been investigated. In the present study, atorvastatin and simvastatin dose-dependently decreased LPL and EL expression as well as Rho, liver X receptor α (LXRα), and nuclear factor κB (NF-κB) activation in THP-1 macrophages. Atorvastatin-reduced LPL and EL expression was only partially recovered by mevalonate cotreatment, indicating that mechanisms independent of reductase inhibition may be present. By contrast, Rho activation by lysophosphatidyl acid further decreased LPL and EL expression in the presence or absence of atorvastatin. Another Rho activator, farnysyl pyrophosphate, decreased EL expression only in the absence of atorvastatin. LXRα activation by T0901317 and 22(R)-hydroxycholesterol not only rescued but also significantly increased LPL expression in the presence and absence of atorvastatin, respectively, whereas LXRα inhibition by 22(S)-hydroxycholesterol decreased LPL expression. By contrast, EL expression was suppressed by LXRα activation in the presence or absence of atorvastatin. NF-κB inhibition by SN50 was associated with an ∼30% reduction of EL expression. Furthermore, atorvastatin treatment significantly attenuated the lipid accumulation in macrophages treated with oxidized LDL. We conclude that atorvastatin reduces LPL and EL expression by reducing the activation of LXRα and NF-κB, respectively. Macrophage-derived lipases are associated with atherosclerosis in human and animal studies. Despite numerous non-lipid-lowering effects of statins, their effect on macrophage LPL and endothelial lipase (EL) expression has not been investigated. In the present study, atorvastatin and simvastatin dose-dependently decreased LPL and EL expression as well as Rho, liver X receptor α (LXRα), and nuclear factor κB (NF-κB) activation in THP-1 macrophages. Atorvastatin-reduced LPL and EL expression was only partially recovered by mevalonate cotreatment, indicating that mechanisms independent of reductase inhibition may be present. By contrast, Rho activation by lysophosphatidyl acid further decreased LPL and EL expression in the presence or absence of atorvastatin. Another Rho activator, farnysyl pyrophosphate, decreased EL expression only in the absence of atorvastatin. LXRα activation by T0901317 and 22(R)-hydroxycholesterol not only rescued but also significantly increased LPL expression in the presence and absence of atorvastatin, respectively, whereas LXRα inhibition by 22(S)-hydroxycholesterol decreased LPL expression. By contrast, EL expression was suppressed by LXRα activation in the presence or absence of atorvastatin. NF-κB inhibition by SN50 was associated with an ∼30% reduction of EL expression. Furthermore, atorvastatin treatment significantly attenuated the lipid accumulation in macrophages treated with oxidized LDL. We conclude that atorvastatin reduces LPL and EL expression by reducing the activation of LXRα and NF-κB, respectively. Macrophages play a pivotal role in the development and progression of atherosclerosis. In response to cellular signals, monocytes adhere to endothelial surfaces and are recruited into the intima of the vascular wall, where they differentiate into macrophages and ultimately transform into foam cells in the presence of excess lipid. Lipid-laden macrophages then become an important source for a variety of cytokines and bioactive products, such as tumor necrosis factor-α, interleukins, chemoattractants, adhesion molecules, and matrix metalloproteases, which collectively can accelerate the progression of the atherosclerotic lesion (1.Lusis A.J. Atherosclerosis.Nature. 2000; 407: 233-241Crossref PubMed Scopus (4735) Google Scholar, 2.Libby P. Inflammation in atherosclerosis.Nature. 2002; 420: 868-874Crossref PubMed Scopus (7017) Google Scholar). By hydrolyzing triglycerides and phospholipids, LPL and endothelial lipase (EL) assume a critical role in lipoprotein metabolism. Through the hydrolysis of triglycerides, LPL simultaneously promotes the clearance of triglyceride-rich lipoproteins and directs lipid into the HDL pool (3.Santamarina-Fojo S. Dugi K.A. Structure, function and role of lipoprotein lipase in lipoprotein metabolism.Curr. Opin. Lipidol. 1994; 5: 117-125Crossref PubMed Scopus (105) Google Scholar). EL has been regarded as an important regulator of HDL metabolism, primarily through its ability to hydrolyze phospholipids (4.Ishida T. Choi S. Kundu R.K. Hirata K. Rubin E.M. Cooper A.D. Quertermous T. Endothelial lipase is a major determinant of HDL level.J. Clin. Invest. 2003; 111: 347-355Crossref PubMed Scopus (273) Google Scholar, 5.Broedl U.C. Maugeais C. Millar J.S. Jin W. Moore R.E. Fuki I.V. Marchadier D. Glick J.M. Rader D.J. Endothelial lipase promotes the catabolism of apoB-containing lipoproteins.Circ. Res. 2004; 94: 1554-1561Crossref PubMed Scopus (69) Google Scholar). The presence of LPL and EL protein has been observed in human atherosclerotic plaques, especially in macrophages (6.O'Brien K.D. Gordon D. Deeb S. Ferguson M. Chait A. Lipoprotein lipase is synthesized by macrophage-derived foam cells in human coronary atherosclerotic plaques.J. Clin. Invest. 1992; 89: 1544-1550Crossref PubMed Scopus (178) Google Scholar, 7.Azumi H. Hirata K. Ishida T. Kojima Y. Rikitake Y. Takeuchi S. Inoue N. Kawashima S. Hayashi Y. Itoh H. et al.Immunohistochemical localization of endothelial cell-derived lipase in atherosclerotic human coronary arteries.Cardiovasc. Res. 2003; 58: 647-654Crossref PubMed Scopus (58) Google Scholar). An accumulating body of evidence also supports a proatherogenic role of macrophage-derived LPL. The LPL level in macrophages derived from subjects with an increased risk of atherosclerosis, such as heterozygous familial hypercholesterolemia or type 2 diabetes, has been reported to be higher compared with that in healthy controls (8.Beauchamp M.C. Letendre E. Renier G. Macrophage lipoprotein lipase expression is increased in patients with heterozygous familial hypercholesterolemia.J. Lipid Res. 2002; 43: 215-222Abstract Full Text Full Text PDF PubMed Google Scholar, 9.Sartippour M.R. Renier G. Upregulation of macrophage lipoprotein lipase in patients with type 2 diabetes: role of peripheral factors.Diabetes. 2000; 49: 597-602Crossref PubMed Scopus (41) Google Scholar). Also, LPL overexpression in macrophages has been associated with an increase in aortic atherosclerosis in cholesterol-fed transgenic rabbits as well as apolipoprotein E (apoE) or LDL receptor knockout mice (10.Ichikawa T. Liang J. Kitajima S. Koike T. Wang X. Sun H. Morimoto M. Shikama H. Watanabe T. Yamada N. et al.Macrophage-derived lipoprotein lipase increases aortic atherosclerosis in cholesterol-fed Tg rabbits.Atherosclerosis. 2005; 179: 87-95Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 11.Wilson K. Fry G.L. Chappell D.A. Sigmund C.D. Medh J.D. Macrophage-specific expression of human lipoprotein lipase accelerates atherosclerosis in transgenic apolipoprotein E knockout mice but not in C57BL/6 mice.Arterioscler. Thromb. Vasc. Biol. 2001; 21: 1809-1815Crossref PubMed Scopus (58) Google Scholar, 12.Babaev V.R. Patel M.B. Semenkovich C.F. Fazio S. Linton M.F. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice.J. Biol. Chem. 2000; 275: 26293-26299Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar). Although conflicting results were reported with regard to the influence of EL in mouse models of atherosclerosis (13.Ishida T. Choi S.Y. Kundu R.K. Spin J. Yamashita T. Hirata K. Kojima Y. Yokoyama M. Cooper A.D. Quertermous T. Endothelial lipase modulates susceptibility to atherosclerosis in apolipoprotein-E-deficient mice.J. Biol. Chem. 2004; 279: 45085-45092Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 14.Ko K.W. Paul A. Ma K. Li L. Chan L. Endothelial lipase modulates HDL but has no effect on atherosclerosis development in apoE−/− and LDLR−/− mice.J. Lipid Res. 2005; 46: 2586-2594Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar), an increase of EL protein was found in human subjects with the metabolic syndrome, and in a separate cohort, plasma EL levels were associated with the concentration of inflammatory markers (15.Paradis M.E. Badellino K.O. Rader D.J. Deshaies Y. Couture P. Archer W.R. Bergeron N. Lamarche B. Endothelial lipase is associated with inflammation in humans.J. Lipid Res. 2006; 47: 2808-2813Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 16.Badellino K.O. Wolfe M.L. Reilly M.P. Rader D.J. Endothelial lipase concentrations are increased in metabolic syndrome and associated with coronary atherosclerosis.PLoS Med. 2006; 3: e22Crossref PubMed Scopus (154) Google Scholar). HMG-CoA reductase inhibitors (satins) effectively reduce cholesterol and apoB-containing lipoprotein levels by blocking the endogenous cholesterol synthesis through the competitive inhibition of HMG-CoA reductase, and they are used extensively in the treatment of hypercholesterolemia. Beyond their lipid-lowering effects, statins are also credited with pleiotropic bioactivities, including the improvement of endothelial dysfunction, the alleviation of inflammation and oxidative stress, and the stabilization of the atherosclerotic plaque (17.Davignon J. Beneficial cardiovascular pleiotropic effects of statins.Circulation. 2004; 109: III39-III43Crossref PubMed Google Scholar). The non-lipid-lowering effects of statins are often attributed to their ability to influence signaling pathways, among which Rho proteins, liver X receptor (LXR), and nuclear factor κB (NF-κB) are most studied (18.Rikitake Y. Liao J.K. Rho GTPases, statins, and nitric oxide.Circ. Res. 2005; 97: 1232-1235Crossref PubMed Scopus (418) Google Scholar, 19.Hernandez-Presa M.A. Ortego M. Tunon J. Martin-Ventura J.L. Mas S. Blanco-Colio L.M. Aparicio C. Ortega L. Gomez-Gerique J. Vivanco F. et al.Simvastatin reduces NF-kappaB activity in peripheral mononuclear and in plaque cells of rabbit atheroma more markedly than lipid lowering diet.Cardiovasc. Res. 2003; 57: 168-177Crossref PubMed Scopus (81) Google Scholar, 20.Wong J. Quinn C.M. Brown A.J. Statins inhibit synthesis of an oxysterol ligand for the liver X receptor in human macrophages with consequences for cholesterol flux.Arterioscler. Thromb. Vasc. Biol. 2004; 24: 2365-2371Crossref PubMed Scopus (132) Google Scholar). There is a relative paucity of knowledge regarding statin influence on lipase expression in macrophages. In clinical studies, the systemic administration of high-dose simvastatin (80 mg daily) was accompanied by a 49% increase in preheparin plasma lipase activity and a 21% increase in LPL activity J.M. The effect of high-dose simvastatin on triglyceride-rich lipoprotein in patients with type 2 Lipid Res. 2006; 47: Full Text Full Text PDF PubMed Scopus Google Scholar). atorvastatin and increased preheparin LPL in type with and the of LPL increase by simvastatin in rabbit was a increase in LPL activity K. Y. A. T. N. H. M. Y. K. and lipoprotein lipase of type 2 with hypercholesterolemia.J. Thromb. 2004; PubMed Scopus Google Scholar, C. M. C. G. M. T. effect of simvastatin and atorvastatin on in synthesis and catabolism in J. PubMed Scopus Google Scholar). of its and may be the major source the increase in plasma LPL statin with increased LPL expression and activity were reported in treated with and atorvastatin A. T. Watanabe F. T. Y. K. lipoprotein lipase expression in Thromb. 2005; PubMed Scopus Google Scholar, L. P. H. of lipoprotein lipase expression in by atorvastatin, a and 2002; PubMed Scopus Google Scholar). the expression of LPL or EL has not been in human macrophages statin In the present study, the expression of LPL and EL in THP-1 macrophages was statin We then further the by which atorvastatin its effect on lipase expression by the signaling molecules, including Rho and The results that atorvastatin macrophage LPL and EL expression by LXRα and respectively. atorvastatin was by and mevalonate and acid were from to Rho from was used to inhibit Rho and 22(R)-hydroxycholesterol were used as and of respectively. SN50 was from for NF-κB THP-1 monocytes were in with and and and used for was a concentration of for to differentiate THP-1 monocytes into macrophages. was then to macrophages concentrations for Macrophages were treated with Rho Rho LXRα T0901317 and or NF-κB SN50 in the absence and presence of atorvastatin. HMG-CoA reductase activity was by the of acid into macrophages 2 of were treated with concentrations of atorvastatin in for then of acid was for an in and and in in lipid was by with of and the cell were in for protein The from were in of and on on which was in acid The of cholesterol and was for protein concentration and with the of cells as Rho activation was used to a Rho 2 macrophage cells treatment were in on for of were then cell by protein was to cell to Rho protein and for with were by and with of in of reducing 2 of and then for and THP-1 monocytes were and treated as with of and was into the and for and then the cells were by and into were for and in of and for 2 with and were and for The NF-κB factor was used for the of NF-κB in nuclear to the necrosis cell and were used for and respectively. activity was used to LPL a as J.S. D. J. H. of lipase and lipoprotein of and Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). were used for the and LPL activity was as an lipase The was to to the and with of LPL or EL were in a to the and of was for was on an with as for for for to and then of for and for was from from LPL and EL were by the of an on most of the lipase was on the cell cell were used for lipase were with and on a of of were for of blocking with were with of mouse a from rabbit EL or and then with mouse or rabbit for were by were and with the or macrophages were in LDL for macrophages were then with and in for with macrophages were with in for and then with macrophages were with for with macrophages were with a macrophages were treated concentrations of atorvastatin in a from 2 to which HMG-CoA reductase activity by 2 and LPL as by the of and a with an increase in atorvastatin with a reduction of and activity was to activity atorvastatin which was decreased by atorvastatin not LPL was decreased by and EL was decreased by atorvastatin The LPL was with the activity a decreased LPL in a with of and of EL protein a of EL with a reduction of and the activity and of LPL and EL were not and no was observed not an atorvastatin concentration of was used in Furthermore, simvastatin to THP-1 macrophages and observed of LPL and EL levels In an to the by which atorvastatin LPL and EL expression in the signaling of the protein Rho, and Rho protein and LXRα levels were dose-dependently decreased by atorvastatin, with a concentration associated with and of NF-κB that atorvastatin decreased NF-κB activity by decreased Rho activation was for the observed reduction in LPL and EL expression atorvastatin used Rho and in an to LPL and EL In the presence of atorvastatin, Rho activation by partially LPL and LPL protein was not significantly as by whereas not increase LPL or protein and further decreased LPL and further the of Rho with LPL treated macrophages with Rho and a Rho in the absence of atorvastatin. Rho activation by and not LPL was associated with a of LPL In with LPL on the was not was to LPL In not LPL or protein levels Although the reduction of activity by Rho or inhibition and was with the reduction associated with treatment The activity and LPL and protein levels may be attributed to the of of the activity for LPL. on Rho by to LPL and a Rho and LPL atorvastatin treatment not be as EL expression was treatment partially rescued EL expression in the presence of atorvastatin of compared with of in but no were observed by not increase EL and protein and to further EL and protein levels In the absence of atorvastatin, Rho activation by and decreased EL and protein whereas Rho inhibition by not EL or protein level results that Rho inhibition was not for the observed reduction in EL expression. the role of LXRα in LPL and EL the LXRα T0901317 and 22(R)-hydroxycholesterol to THP-1 macrophages in the presence and absence of atorvastatin. the inhibition of LPL and protein by atorvastatin was rescued by the LXRα T0901317 and of and was partially recovered by the 22(R)-hydroxycholesterol and of LXRα activation by and and significantly increased LPL and activity and and and in the absence of atorvastatin Furthermore, LXRα inhibition by decreased LPL in the presence and absence of atorvastatin the that LPL is by LXRα By contrast, LXRα activation was not to the effects of atorvastatin on EL expression. with the 22(R)-hydroxycholesterol the effect of atorvastatin, further EL and with only and of levels whereas the T0901317 not effects in the presence of atorvastatin. In the absence of atorvastatin, LXRα activation by T0901317 and 22(R)-hydroxycholesterol suppressed EL expression by and respectively, and EL protein by and further the by which atorvastatin reduces EL then the role of macrophages were treated with the NF-κB SN50 treatment in a reduction of NF-κB EL expression was by with a in protein as observed with In of the effect of atorvastatin on NF-κB, is to that atorvastatin may EL through decreased NF-κB In the effects of Rho and LXRα activation on NF-κB were also NF-κB activity was to from to Rho activation by and whereas Rho inhibition by not the NF-κB level Furthermore, LXRα activation by T0901317 and 22(R)-hydroxycholesterol the effect as Rho activation on NF-κB with and results may in the of Rho and LXRα EL expression. the effects of atorvastatin on foam cell macrophages were treated with oxidized LDL for in the presence and absence of atorvastatin. was that macrophages a of lipid compared with in which only lipid were in the cells that atorvastatin treatment can inhibit the development of macrophage-derived foam The non-lipid-lowering effects of statins been studied in numerous cell models for a of the effects of statins on lipase expression in macrophages not been We in the present that LPL and EL expression in human macrophages were markedly by effect may to statins, as the of LPL and EL were also observed simvastatin statins are competitive inhibitors of HMG-CoA reductase, the of a variety of cholesterol is In such as and been to the and activation of Rho G. M.C. M. J. E. of in the of with 2001; PubMed Scopus Google Scholar). cholesterol is a to statins also endogenous of LXRα J. Quinn C.M. Brown A.J. Statins inhibit synthesis of an oxysterol ligand for the liver X receptor in human macrophages with consequences for cholesterol flux.Arterioscler. Thromb. Vasc. Biol. 2004; 24: 2365-2371Crossref PubMed Scopus (132) Google Scholar). LXRα can be L. J.L. P. of the human liver X receptor Biol. 2001; 21: PubMed Scopus Google Scholar), the of LXRα to oxysterol reduction statin treatment to decreased protein as in of was for the observed of LPL and EL in THP-1 a of and inhibitors of We observed that activation of Rho not the effects on lipase by atorvastatin treatment in a further in lipase expression. treatment was to only partially LPL and EL levels in the presence of atorvastatin, that HMG-CoA effects may that statins can effects that to be M. B. M. inhibition of expression by atorvastatin in human endothelial Thromb. Vasc. Biol. 2002; PubMed Scopus Google Scholar, G. K. T. J. C. S. Y. Statins inhibit function by to a Med. 2001; PubMed Scopus Google Scholar). In has been reported that effects may be by the ability of statins to to a to an inflammatory response in G. K. T. J. C. S. Y. Statins inhibit function by to a Med. 2001; PubMed Scopus Google Scholar). Furthermore, Rho inhibition by not LPL or EL that Rho is not the for atorvastatin on lipase expression in macrophages. is that the effects of Rho on lipase expression may be through the factor which with the on of for including and in the 1992; Google Scholar). The for has been and in the human LPL of a factor in the human lipoprotein lipase 1992; PubMed Scopus Google Scholar). on the its activity be in and in N. N. of the and of PubMed Scopus Google Scholar, and is in by J. PubMed Scopus Google Scholar). with a in low plasma LPL activity by an of J.D. Deeb in the of the lipoprotein lipase in a with familial and low LPL PubMed Scopus Google Scholar). Furthermore, treated with tumor necrosis factor-α, a expression of LPL to the of an from the on the LPL necrosis of and an protein to the lipoprotein lipase in Clin. Invest. PubMed Scopus Google Scholar). Rho activation may to the of and its from the to the LPL The for is also found the EL D. C. Wang The factor is a Res. 2005; PubMed Scopus Google Scholar), but its has not been investigated. LXRα activation and increased LPL and activity in the absence of atorvastatin and rescued LPL in the presence of atorvastatin, whereas LXRα inhibition decreased LPL in the presence and absence of atorvastatin. with et Y. K. D.J. of lipoprotein lipase by the oxysterol and Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google reported that a response is present in the and 2 in the LPL and that expression be by Furthermore, mice a cholesterol or an a increase in LPL expression in liver and whereas a response of LPL expression was observed in mice Y. K. D.J. of lipoprotein lipase by the oxysterol and Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). that atorvastatin may reduce the expression of LPL by LXRα By contrast, LXRα activation was associated with a in EL expression in the presence or absence of atorvastatin. has been that the LXRα T0901317 suppressed EL expression in human endothelial whereas 22(R)-hydroxycholesterol no effect M. P. F. X receptor and X receptor the expression of in lipid in human endothelial J. Med. 2005; Google Scholar). of in EL the and protein levels in endothelial cells A. A. A. S. S. Rader D.J. E. W. expression of endothelial lipase by endothelial cells the 2005; 94: PubMed Scopus Google Scholar). An LXRα response has not been the EL the of the influence of LXRα on expression In the receptor also reduces EL expression. of LXRα and L. F. C. H. J. J. K. X. H. of and with 2005; PubMed Scopus Google Scholar), the effect of EL inhibition by LXRα be by LXRα not to be for EL atorvastatin NF-κB, factor associated with EL expression. has been reported that for NF-κB were present in the of of the EL and a with the EL in cells the by NF-κB S. H. A. T. NF-kappaB controls the response in endothelial evidence for the of a Res. 2005; PubMed Scopus Google Scholar). In the present study, in THP-1 macrophages that atorvastatin The effect of statins on NF-κB has been observed with and simvastatin in human vascular endothelial and cells J. N. G. W. Wang W. reduces nuclear factor activation by protein in human vascular endothelial 2005; PubMed Scopus Google Scholar, D. A. M. B. M. modulates adhesion expression in human endothelial 2004; PubMed Scopus Google Scholar, W. J. M. M.P. J. F. HMG-CoA reductase inhibitors inflammatory in human endothelial and vascular Thromb. Vasc. Biol. 2003; PubMed Scopus Google Scholar). Furthermore, has been that the ability of statins to as well as to the of endothelial nitric inhibit NF-κB by the and stabilization of W. J. M. M.P. J. F. HMG-CoA reductase inhibitors inflammatory in human endothelial and vascular Thromb. Vasc. Biol. 2003; PubMed Scopus Google Scholar). In the present study, inhibition of NF-κB by SN50 in decreased EL and protein with NF-κB activation by and tumor necrosis was to the expression of EL and protein in human endothelial whereas the NF-κB SN50 attenuated response W. Sun Marchadier D. E. Glick J.M. Rader D.J. Endothelial cells lipase and in response to cytokines as a of endothelial Res. 2003; PubMed Scopus Google Scholar). that the treatment of Rho and LXRα to the reduction of NF-κB in Rho and LXRα activation EL By contrast, NF-κB to be critical in the of as NF-κB inhibition by SN50 not of LPL expression not and a NF-κB has not been in the of the LPL in atorvastatin treatment attenuated macrophage-derived foam cell LPL was to be to macrophage-derived foam cell formation V.R. Patel M.B. Semenkovich C.F. Fazio S. Linton M.F. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice.J. Biol. Chem. 2000; 275: 26293-26299Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar, V.R. Fazio S. Semenkovich C.F. Linton M.F. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in Clin. Invest. PubMed Scopus Google Scholar). In EL also a role in LDL independent of its activity I.V. N. Jin W. Marchadier Millar J.S. Glick J.M. Rader D.J. endothelial lipase and cellular of plasma lipoproteins Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). from a EL expression and LDL and in THP-1 macrophages the cholesterol accumulation observed in THP-1 macrophages may be in to the expression of EL and LPL. effects of statins that been such as decreased expression of lipoprotein A. M. T. K. S. K. A. K. M. macrophage foam cell formation through Thromb. Vasc. Biol. 2005; PubMed Scopus Google Scholar, B. L. N. S. T. M. in patients cellular of by 2002; Full Text Full Text PDF PubMed Scopus Google Scholar), also influence foam cell The in the present signaling for the of lipase expression in THP-1 macrophages that the expression of LPL and EL is by LXRα and NF-κB, respectively, whereas NF-κB is by Rho and treatment LPL and EL expression in THP-1 macrophages by reducing the formation of oxysterol LXRα and NF-κB, respectively, which to the ability of atorvastatin treatment to lipid accumulation in macrophages. the ability of atorvastatin to LPL and EL expression in THP-1 macrophages may be an that from the development of atherosclerosis. was by from the of and the and of and is a of the of is the of a and of

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.