sterol o acyltransferase

Summary

Summary: An enzyme that catalyzes the formation of cholesterol esters by the direct transfer of the fatty acid group from a fatty acyl CoA derivative. This enzyme has been found in the adrenal gland, gonads, liver, intestinal mucosa, and aorta of many mammalian species. EC 2.3.1.26.

Top Publications

  1. Cases S, Novak S, Zheng Y, Myers H, Lear S, Sande E, et al. ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase. Its cloning, expression, and characterization. J Biol Chem. 1998;273:26755-64 pubmed
    ..The identification and cloning of ACAT-2 will facilitate molecular approaches to understanding the role of ACAT enzymes in mammalian biology. ..
  2. Meuwese M, de Groot E, Duivenvoorden R, Trip M, Ose L, Maritz F, et al. ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial. JAMA. 2009;301:1131-9 pubmed publisher
    ..clinicaltrials.gov Identifier: NCT00151788. ..
  3. Maung K, Miyazaki A, Nomiyama H, Chang C, Chang T, Horiuchi S. Induction of acyl-coenzyme A:cholesterol acyltransferase-1 by 1,25-dihydroxyvitamin D(3) or 9-cis-retinoic acid in undifferentiated THP-1 cells. J Lipid Res. 2001;42:181-7 pubmed
    ..0-fold by using 100 nM 1,25-(OH)(2)D(3), and 1.8-fold by using 1 microM 9-cis-RA. Together, our results suggest that 1,25-(OH)(3) participates in ACAT-1 gene expression during the monocyte-macrophage differentiation process. ..
  4. Seo T, Oelkers P, Giattina M, Worgall T, Sturley S, Deckelbaum R. Differential modulation of ACAT1 and ACAT2 transcription and activity by long chain free fatty acids in cultured cells. Biochemistry. 2001;40:4756-62 pubmed
    ..In contrast, HepG2 and ACAT2 microsomes utilized linolenoyl CoA as well. We conclude that FFAs increase ACAT1 mRNA levels in a cell specific manner, and furthermore that the ACAT reactions exhibit differential FFA utilization. ..
  5. Nissen S, Tuzcu E, Brewer H, Sipahi I, Nicholls S, Ganz P, et al. Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med. 2006;354:1253-63 pubmed
    ..ACAT inhibition is not an effective strategy for limiting atherosclerosis and may promote atherogenesis. (ClinicalTrials.gov number, NCT00268515.). ..
  6. Chinetti G, Lestavel S, Fruchart J, Clavey V, Staels B. Peroxisome proliferator-activated receptor alpha reduces cholesterol esterification in macrophages. Circ Res. 2003;92:212-7 pubmed
    ..In conclusion, our results identify a role for PPARalpha in the control of cholesterol esterification in macrophages, resulting in an enhanced availability of FC for efflux through the ABCA1 pathway. ..
  7. Tardif J, Gregoire J, L Allier P, Anderson T, Bertrand O, Reeves F, et al. Effects of the acyl coenzyme A:cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions. Circulation. 2004;110:3372-7 pubmed
    ..8%, 9.1%, and 10.9% in the respective avasimibe groups (P<0.05 in all groups). Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS. This ACAT inhibitor also caused a mild increase in LDL cholesterol. ..
  8. Lee J, Carr T. Dietary fatty acids regulate acyl-CoA:cholesterol acyltransferase and cytosolic cholesteryl ester hydrolase in hamsters. J Nutr. 2004;134:3239-44 pubmed
    ..The data suggest that cholesterolemic effects of individual dietary fatty acids can be achieved through their independent modulation of pathways regulating assembly and secretion of apoB(100)-containing particles. ..
  9. Uelmen P, Oka K, Sullivan M, Chang C, Chang T, Chan L. Tissue-specific expression and cholesterol regulation of acylcoenzyme A:cholesterol acyltransferase (ACAT) in mice. Molecular cloning of mouse ACAT cDNA, chromosomal localization, and regulation of ACAT in vivo and in vitro. J Biol Chem. 1995;270:26192-201 pubmed
    ..Two transfected Chinese hamster ovary cell lines that expressed the mouse ACAT transgene regained the ability to esterify cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) ..

More Information

Publications62

  1. Tao J, Ruan X, Li H, Li X, Li X. Lipids-induced apoptosis is aggravated by acyl-coenzyme A: cholesterol acyltransferase inhibitor. Chin Med Sci J. 2010;25:76-84 pubmed
    ..Lipids could induce apoptosis, accompanied by increase of intracellular free cholesterol content, which could be augmented by ACATI, suggesting that insults resulting in ER free cholesterol rise might be the initiator of apoptosis. ..
  2. Moore E, Napolitano M, Prosperi A, Avella M, Suckling K, Bravo E, et al. Incorporation of lycopene into chylomicron remnant-like particles enhances their induction of lipid accumulation in macrophages. Biochem Biophys Res Commun. 2003;312:1216-9 pubmed
    ..These findings suggest that lycopene from the diet may promote, rather than retard, lipid accumulation in macrophages during its transport in the blood in chylomicron remnants. ..
  3. Namatame I, Tomoda H, Ishibashi S, Omura S. Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophages. Proc Natl Acad Sci U S A. 2004;101:737-42 pubmed
    ..Beauveriolides I and III are the first microbial cyclodepsipeptides having an in vivo antiatherosclerotic effect and show promise as potential lead compounds for antiatherosclerotic agents. ..
  4. Lee J, Bok S, Park Y, Lee M, Choi M. 4-hydroxycinnamate lowers plasma and hepatic lipids without changing antioxidant enzyme activities. Ann Nutr Metab. 2003;47:144-51 pubmed
    ..These results indicate that 4-(OH)-C was effective in lowering the plasma cholesterol and hepatic lipids. ..
  5. Hori M, Miyazaki A, Tamagawa H, Satoh M, Furukawa K, Hakamata H, et al. Up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 by transforming growth factor-beta1 during differentiation of human monocytes into macrophages. Biochem Biophys Res Commun. 2004;320:501-5 pubmed
    ..Since TGF-beta1 is expressed in human atherosclerotic lesions, the current results suggest that ACAT-1 expression in monocytes infiltrating from the circulation to vascular walls may be enhanced by pre-existing TGF-beta1. ..
  6. Fujimoto T. [Lipid droplet as an independent organelle]. Seikagaku. 2004;76:578-84 pubmed
  7. Kushwaha R, Rosillo A, Rodriguez R, McGill H. Expression levels of ACAT1 and ACAT2 genes in the liver and intestine of baboons with high and low lipemic responses to dietary lipids. J Nutr Biochem. 2005;16:714-21 pubmed
    ..These results suggest that differences in ACAT1 expression may affect plasma cholesterol concentration and partly affect diet-induced hyperlipidemia. ..
  8. Benfatti F, Cardillo G, Gentilucci L, Tolomelli A. Synthesis and biological evaluation of unprecedented classes of spiro-beta-lactams and azido-beta-lactams as acyl-CoA:cholesterol acyltransferase inhibitors. Bioorg Med Chem Lett. 2007;17:1946-50 pubmed
    ..The potential of these particular beta-lactams as biologically active compounds has been confirmed by the results obtained in ACAT inhibition assays. ..
  9. Suguro T, Watanabe T, Kanome T, Kodate S, Hirano T, Miyazaki A, et al. Serotonin acts as an up-regulator of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-macrophages. Atherosclerosis. 2006;186:275-81 pubmed
  10. Watanabe T, Suguro T, Kanome T, Sakamoto Y, Kodate S, Hagiwara T, et al. Human urotensin II accelerates foam cell formation in human monocyte-derived macrophages. Hypertension. 2005;46:738-44 pubmed
  11. Ahn E, Bang M, Song M, Park M, Kim H, Kwon B, et al. Cytotoxic and ACAT-inhibitory sesquiterpene lactones from the root of Ixeris dentata forma albiflora. Arch Pharm Res. 2006;29:937-41 pubmed
    ..Compounds 1, 2 and 7 revealed relatively high cytotoxicities on human colon carcinoma cell and lung adenocarcinoma cell, while compounds 5 and 7 showed acyl-CoA: cholesterol acyltransferase (ACAT) inhibitory activity. ..
  12. Huang G, Shifman S, Valdar W, Johannesson M, Yalcin B, Taylor M, et al. High resolution mapping of expression QTLs in heterogeneous stock mice in multiple tissues. Genome Res. 2009;19:1133-40 pubmed publisher
    ..Approximately one third of cis-acting eQTLs and one half of trans-acting eQTLs are tissue specific. We have created an important systems biology resource for the genetic analysis of complex traits in a key model organism. ..
  13. He P, Mei C, Cheng B, Liu W, Wang Y, Wan J. [Chlamydia pneumoniae induces THP-1-derived foam cell formation by up-regulating the expression of acyl-coenzyme A: cholesterol acyltransferase 1]. Zhonghua Xin Xue Guan Bing Za Zhi. 2009;37:430-5 pubmed
    ..05). Chlamydia pneumoniae induces THP-1-derived foam cell formation by up-regulating the expression of ACAT1. ..
  14. Parini P, Davis M, Lada A, Erickson S, Wright T, Gustafsson U, et al. ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver. Circulation. 2004;110:2017-23 pubmed
    ..The data suggest that in diseases in which dysregulation of cholesterol metabolism occurs, such as hypercholesterolemia and atherosclerosis, ACAT2 should be considered a target for prevention and treatment. ..
  15. Ogawa H, Mochizuki S. Hypocholesterolaemic effects of an ethanol precipitate of Kabosu juice in stroke-prone spontaneously hypertensive rats fed a cholesterol-free diet. Clin Exp Pharmacol Physiol. 2003;30:532-6 pubmed
  16. Giovannoni M, Piaz V, Vergelli C, Barlocco D. Selective ACAT inhibitors as promising antihyperlipidemic, antiathero-sclerotic and anti-Alzheimer drugs. Mini Rev Med Chem. 2003;3:576-84 pubmed
    ..Finally, ACAT inhibitors have recently been proposed for the treatment of Alzheimer's disease. ..
  17. Marzal Casacuberta A, Blanco Vaca F, Ishida B, Julve Gil J, Shen J, Calvet Márquez S, et al. Functional lecithin:cholesterol acyltransferase deficiency and high density lipoprotein deficiency in transgenic mice overexpressing human apolipoprotein A-II. J Biol Chem. 1996;271:6720-8 pubmed
    ..The LCAT and HDL deficiencies observed in this study indicate that apoA-II plays a dynamic role in the regulation of plasma HDL metabolism. ..
  18. Lin S, Cheng D, Liu M, Chen J, Chang T. Human acyl-CoA:cholesterol acyltransferase-1 in the endoplasmic reticulum contains seven transmembrane domains. J Biol Chem. 1999;274:23276-85 pubmed
    ..The results show that human ACAT-1 in the ER contains seven transmembrane domains. ..
  19. Toma L, Giovannoni M, Vergelli C, Dal Piaz V, Kwon B, Kim Y, et al. Novel 3-arylamino- and 3-cycloalkylamino-5, 6-diphenyl-pyridazines active as ACAT inhibitors. Arch Pharm (Weinheim). 2002;335:563-6 pubmed
    ..Substitution of the 3-alkylamino chain with a phenylamino group maintains activity. In contrast, the presence of either substituents on the phenylamino group or aliphatic rings having more or less than six carbon atoms lowers it. ..
  20. Tauchi Y, Yoshimi A, Shirahase H, Sato J, Ito K, Morimoto K. Inhibitory effect of acyl-CoA:cholesterol acyltransferase inhibitor-low density lipoprotein complex on experimental atherosclerosis. Biol Pharm Bull. 2003;26:73-8 pubmed
    ..Therefore, KV-LDL complex may be useful as a drug-carrier complex in antiatherosclerotic therapy. ..
  21. de Medina P, Payré B, Bernad J, Bosser I, Pipy B, Silvente Poirot S, et al. Tamoxifen is a potent inhibitor of cholesterol esterification and prevents the formation of foam cells. J Pharmacol Exp Ther. 2004;308:1165-73 pubmed
    ..This work constitutes the first evidence that tamoxifen is an inhibitor of ACAT and foam cell formation at therapeutic doses and that this may account for its atheroprotective action. ..
  22. Francis G, Tsujita M, Terry T. Apolipoprotein AI efficiently binds to and mediates cholesterol and phospholipid efflux from human but not rat aortic smooth muscle cells. Biochemistry. 1999;38:16315-22 pubmed
    ..The marked difference in apoAI binding to human and rat arterial SMC provides an excellent model to study the nature of the apoAI-cell binding interaction. ..
  23. Brown J, Bell T, Alger H, Sawyer J, Smith T, Kelley K, et al. Targeted depletion of hepatic ACAT2-driven cholesterol esterification reveals a non-biliary route for fecal neutral sterol loss. J Biol Chem. 2008;283:10522-34 pubmed publisher
    ..Collectively, these studies provide the first insight into the hepatic itinerary of cholesterol when cholesterol esterification is inhibited only in the liver, and provide evidence for a novel non-biliary route of fecal sterol loss. ..
  24. Chiwata T, Aragane K, Fujinami K, Kojima K, Ishibashi S, Yamada N, et al. Direct effect of an acyl-CoA:cholesterol acyltransferase inhibitor, F-1394, on atherosclerosis in apolipoprotein E and low density lipoprotein receptor double knockout mice. Br J Pharmacol. 2001;133:1005-12 pubmed
    ..These results indicate that ACAT may be primarily responsible for lipid accumulation in atherosclerotic lesions, and that its inhibition diminishes the lipid deposition via a direct effect on macrophages in the arterial wall. ..
  25. Song M, Nigussie F, Jeong T, Lee C, Regassa F, Markos T, et al. Phenolic compounds from the roots of Lindera fruticosa. J Nat Prod. 2006;69:853-5 pubmed
    ..These compounds were evaluated for their inhibitory effects on human acyl-CoA:cholesterol acyltransferase activity and on the in vitro oxidation of low-density lipoprotein...
  26. Nakazawa J, Yajima J, Usui T, Ueki M, Takatsuki A, Imoto M, et al. A novel action of terpendole E on the motor activity of mitotic Kinesin Eg5. Chem Biol. 2003;10:131-7 pubmed
    ..Taken together, we demonstrate that TerE is a novel Eg5 inhibitor isolated from a fungal strain. ..
  27. Rudel L, Lee R, Parini P. ACAT2 is a target for treatment of coronary heart disease associated with hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2005;25:1112-8 pubmed
    ..At the present time, the bulk of the available data suggest that the strategy seeming to bear the most potential for treatment of coronary heart disease associated with hypercholesterolemia would be to specifically inhibit ACAT2. ..
  28. Labute P, Nilar S, Williams C. A probabilistic approach to high throughput drug discovery. Comb Chem High Throughput Screen. 2002;5:135-45 pubmed
    ..The results suggest that the methodology is capable of selecting combinatorial substituents that lead to active compounds starting with binary (pass/fail) activity measurements. ..
  29. Francis G, Oram J, Heinecke J, Bierman E. Oxidative tyrosylation of HDL enhances the depletion of cellular cholesteryl esters by a mechanism independent of passive sterol desorption. Biochemistry. 1996;35:15188-97 pubmed
  30. Huttunen H, Kovacs D. ACAT as a drug target for Alzheimer's disease. Neurodegener Dis. 2008;5:212-4 pubmed publisher
    ..Here, we discuss data supporting ACAT inhibition as a strategy to treat Alzheimer's disease. ..
  31. Seo T, Velez Carrasco W, Qi K, Hall M, Worgall T, Johnson R, et al. Selective uptake from LDL is stimulated by unsaturated fatty acids and modulated by cholesterol content in the plasma membrane: role of plasma membrane composition in regulating non-SR-BI-mediated selective lipid transfer. Biochemistry. 2002;41:7885-94 pubmed
    ..Moreover, in conditions where elevated plasma FFA occur, SU from LDL can be an important mechanism for cholesterol delivery in vivo. ..
  32. Strömsten A, von Bahr S, Bringman S, Saeki M, Sahlin S, Bjorkhem I, et al. Studies on the mechanism of accumulation of cholesterol in the gallbladder mucosa. Evidence that sterol 27-hydroxylase is not a pathogenetic factor. J Hepatol. 2004;40:8-13 pubmed
    ..The pathogenesis of cholesterolosis may be multifactorial, but is not caused by reduced efflux of cholesterol due to a defect sterol 27-hydroxylase mechanism. ..
  33. Vaziri N, Liang K. Effects of HMG-CoA reductase inhibition on hepatic expression of key cholesterol-regulatory enzymes and receptors in nephrotic syndrome. Am J Nephrol. 2004;24:606-13 pubmed
    ..HMG-CoA reductase inhibition improved hepatic LDL and HDL receptor deficiencies, and ameliorated the associated hyperlipidemia in the nephrotic rats. ..
  34. Sethi A, Sampson M, Warnick R, Muniz N, Vaisman B, Nordestgaard B, et al. High pre-beta1 HDL concentrations and low lecithin: cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol. Clin Chem. 2010;56:1128-37 pubmed publisher
  35. Fujiwara Y, Kiyota N, Hori M, Matsushita S, Iijima Y, Aoki K, et al. Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT. Arterioscler Thromb Vasc Biol. 2007;27:2400-6 pubmed
    ..Our study provides the first evidence that purified esculeogenin A significantly suppresses the activity of ACAT protein and leads to reduction of atherogenesis. ..
  36. Brown W. Promising therapies for cholesterol reduction. Manag Care. 2002;11:10-4 pubmed
  37. Sudhahar V, Ashokkumar S, Varalakshmi P. Effect of lupeol and lupeol linoleate on lipemic--hepatocellular aberrations in rats fed a high cholesterol diet. Mol Nutr Food Res. 2006;50:1212-9 pubmed
    ..Therefore, it can be concluded that triterpenes treatment afforded substantial protection against the anomalies, which are manifested during the early stage of hypercholesterolemic atherogenesis. ..
  38. Kruth H, Ifrim I, Chang J, Addadi L, Perl Treves D, Zhang W. Monoclonal antibody detection of plasma membrane cholesterol microdomains responsive to cholesterol trafficking. J Lipid Res. 2001;42:1492-500 pubmed
    ..For the first time, cholesterol microdomains have been visualized that function in cholesterol trafficking to and from the plasma membrane. ..
  39. ADAMEOVA A, Kuzelova M, Faberova V, Svec P. The hypolipidemic effect of a new ACAT inhibitor, VULM 1457, in diabetic-hypercholesterolaemic rats. Pharmazie. 2005;60:714-5 pubmed
    ..VULM 1457, with a slight influence on triglyceride levels, significantly reduced plasma and hepatic cholesterol concentrations (p < 0.05, p < 0.001; respectively) in the diabetic-hypercholesterolaemic rats. ..
  40. Terasaka N, Miyazaki A, Kasanuki N, Ito K, Ubukata N, Koieyama T, et al. ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice. Atherosclerosis. 2007;190:239-47 pubmed
    ..These data indicate that CS-505 can reduce and stabilize atherosclerotic lesions. This antiatherosclerotic activity is exerted via both cholesterol lowering and direct ACAT inhibition in plaque macrophages. ..
  41. An S, Cho K, Lee W, Lee J, Paik Y, Jeong T. A critical role for the histidine residues in the catalytic function of acyl-CoA:cholesterol acyltransferase catalysis: evidence for catalytic difference between ACAT1 and ACAT2. FEBS Lett. 2006;580:2741-9 pubmed
  42. Ruan X, Moorhead J, Tao J, Ma K, Wheeler D, Powis S, et al. Mechanisms of dysregulation of low-density lipoprotein receptor expression in vascular smooth muscle cells by inflammatory cytokines. Arterioscler Thromb Vasc Biol. 2006;26:1150-5 pubmed
    ..The implication of these findings is that inflammatory cytokines may contribute to intracellular LDL accumulation without previous modification of the lipoprotein. ..
  43. Buhman K, Accad M, Novak S, Choi R, Wong J, Hamilton R, et al. Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat Med. 2000;6:1341-7 pubmed
    ..Our results indicate that ACAT2 has an important role in the response to dietary cholesterol, and suggest that ACAT2 inhibition may be a useful strategy for treating hypercholesterolemia or cholesterol gallstones. ..
  44. Munoz Muriedas J, Perspicace S, Bech N, Guccione S, Orozco M, Luque F. Hydrophobic molecular similarity from MST fractional contributions to the octanol/water partition coefficient. J Comput Aided Mol Des. 2005;19:401-19 pubmed
  45. Ohnuma S, Muraoka M, Ioriya K, Ohashi N. Synthesis and structure-activity relationship studies on a novel series of naphthylidinoylureas as inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT). Bioorg Med Chem Lett. 2004;14:1309-11 pubmed
    ..The most potent compound, SM-32504 (3m), decreased the serum cholesterol level significantly in a high fat and high cholesterol-fed mouse model. ..
  46. Schønberg S, Lundemo A, Fladvad T, Holmgren K, Bremseth H, Nilsen A, et al. Closely related colon cancer cell lines display different sensitivity to polyunsaturated fatty acids, accumulate different lipid classes and downregulate sterol regulatory element-binding protein 1. FEBS J. 2006;273:2749-65 pubmed
    ..Our results demonstrate cell-specific mechanisms for the processing and storage of cytotoxic PUFAs in closely related cell lines, and suggest downregulation of nSREBP1 as a possible contributor to the growth inhibitory effect of DHA. ..
  47. Yu Poth S, Yin D, Kris Etherton P, Zhao G, Etherton T. Long-chain polyunsaturated fatty acids upregulate LDL receptor protein expression in fibroblasts and HepG2 cells. J Nutr. 2005;135:2541-5 pubmed
    ..Furthermore, the effects of the fatty acids appeared to be independent of any change in SREBP-1 protein. ..
  48. Tomoda H, Doi T. Discovery and combinatorial synthesis of fungal metabolites beauveriolides, novel antiatherosclerotic agents. Acc Chem Res. 2008;41:32-9 pubmed
    ..Efforts of further analogue synthesis would make it possible to obtain highly selective ACAT1/ACAT2 inhibitors. ..
  49. Chroni A, Duka A, Kan H, Liu T, Zannis V. Point mutations in apolipoprotein A-I mimic the phenotype observed in patients with classical lecithin:cholesterol acyltransferase deficiency. Biochemistry. 2005;44:14353-66 pubmed
    ..The findings indicate a critical contribution of residue 160 of apoA-I to the in vivo activity of LCAT and the subsequent maturation of HDL and explain the low HDL levels in heterozygous subjects carrying this mutation. ..
  50. Liang K, Vaziri N. HMG-CoA reductase, cholesterol 7alpha-hydroxylase, LCAT, ACAT, LDL receptor, and SRB-1 in hereditary analbuminemia. Kidney Int. 2003;64:192-8 pubmed
    ..Unlike nephrotic syndrome, which causes severe LDL receptor, HDL receptor, and LCAT deficiencies, hereditary analbuminemia does not affect these proteins. ..
  51. Hirakawa Y, Shimokawa H. [Lipid-lowering drugs]. Nihon Yakurigaku Zasshi. 2001;118:389-95 pubmed
    ..In this review, characteristics of these new lipid-lowering drugs will be discussed. ..
  52. Ioriya K, Nishimura T, Ohashi N. Effect of SMP-500, a novel ACAT inhibitor, on hepatic cholesterol disposition in rats. Lipids. 2002;37:395-400 pubmed
    ..SMP-500 reduced the serum TG level in sucrose-fed rats. From these results, one may hypothesize that the suppression of hepatic VLDL secretion probably plays an important role on both cholesterol- and TG-lowering effects of SMP-500. ..
  53. Kharbanda R, Wallace S, Walton B, Donald A, Cross J, Deanfield J. Systemic Acyl-CoA:cholesterol acyltransferase inhibition reduces inflammation and improves vascular function in hypercholesterolemia. Circulation. 2005;111:804-7 pubmed
    ..This may be a novel therapeutic strategy to target vascular inflammation and endothelial dysfunction in atherosclerosis. ..