Cholesterol synthesis inhibition elicits an integrated molecular response in human livers including decreased ACAT2

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 28, Issue 6, 2008, Pages 1200-1206

  Parini, Paolo ^a,b   Gustafsson, Ulf ^a   Davis, Matt A ^b   Larsson, Lilian ^a   Einarsson, Curt ^a   Wilson, Martha ^b   Rudling, Mats ^a   Tomoda, Hiroshi ^c   Omura, Satoshi ^c   Sahlin, Staffan ^a   Angelin, Bo ^a   Rudel, Lawrence L ^b   Eriksson, Mats ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b WAKE FOREST SCHOOL OF MEDICINE   (United States)

^c KITASATO UNIVERSITY   (Japan)

Author keywords

Apolipoproteins; Cholesterol; Lipoprotein; Liver; Receptors

Indexed keywords

ABC TRANSPORTER A1; ACETYL COENZYME A ACYLTRANSFERASE; ACETYL COENZYME A ACYLTRANSFERASE 2; APOLIPOPROTEIN A1; APOLIPOPROTEIN E; ATORVASTATIN; FLUINDOSTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; LATHOSTEROL; LIVER PROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR; MESSENGER RNA; PLACEBO; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN; CHOLESTEROL; CHOLESTEROL ACYLTRANSFERASE; HEPTANOIC ACID DERIVATIVE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INDOLE DERIVATIVE; MONOUNSATURATED FATTY ACID; PYRROLE DERIVATIVE; STEROL O ACYLTRANSFERASE 2; STEROL O-ACYLTRANSFERASE 2; VERY LOW DENSITY LIPOPROTEIN CHOLESTEROL;

ADULT; ARTICLE; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL METABOLISM; CHOLESTEROL SYNTHESIS; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; FEMALE; GALLSTONE; HUMAN; HUMAN TISSUE; HYPERCHOLESTEROLEMIA; LIPOPROTEIN BLOOD LEVEL; LIVER BIOPSY; LIVER MICROSOME METABOLISM; MALE; METABOLIC INHIBITION; PREOPERATIVE TREATMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL; THERAPY EFFECT; TREATMENT OUTCOME; TREATMENT RESPONSE; BIOPSY; BLOOD; CONTROLLED STUDY; DRUG EFFECT; LIVER; METABOLISM; MIDDLE AGED; PATHOLOGY;

APOLIPOPROTEINS E; BIOPSY; CHOLESTEROL; CHOLESTEROL, VLDL; FATTY ACIDS, MONOUNSATURATED; FEMALE; HEPTANOIC ACIDS; HUMANS; HYDROXYMETHYLGLUTARYL COA REDUCTASES; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INDOLES; LIVER; MALE; MIDDLE AGED; PYRROLES; RECEPTORS, LDL; RNA, MESSENGER; STEROL O-ACYLTRANSFERASE;

EID: 44849117519     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/ATVBAHA.107.157172     Document Type: Article

References (31)

1. Gotto AM Jr. Management of dyslipidemia. Am J Med. 2002;112 Suppl 8A:10S.18S.
2. Brown MS, Goldstein JL. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell, 1997;89:331-340.
3. Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen M.J, Holme I, Larsen ML, Bendiksen FS, Lindahl C, Szarek M, Tsai J. High-dose atorvastatin vs usual-dose simvastatin for secondary pre vention after myocardial infarction: die IDEAL study: a randomized controlled trial. JAMA. 2005;294:2437-2445.
4. Lawrence JM, Reid J, Taylor GJ, Stirling C, Reckless JP. The effect of high dose atorvastatin therapy on lipids and lipoprotein subfractions in overweight patients with type 2 diabetes. Atherosclerosis. 2004;174: 141-149.
5. van der Harst P, Voors AA, van Veldhuisen DJ. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 351:714-717, 2004; author reply 714-717.
6. Parini P, Davis M, Lada AT, Erickson SK, Wright LT, Gustafsson U, Sahlin S, Einarsson C, Eriksson M, Angelin B, Tomoda H, Omura S, Willingham MC, Rudel LL. ACAT2 is localized to hepatocytes and is die major cholesterol, esterifying enzyme in human liver. Circulation. 2004; 110:2017-2023.
7. Rudel LL, Lee RG, Parini P. ACAT2 is a target for treatment of coronary heart disease associated with hypercholesterolemia. Arterioscler Thromb Vase Biol. 2005;25:1112.1118.
8. Rigotti A, Miettinen HE, Krieger M. The role of die high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues. Endocr Rev. 2003;24:357-387.
9. Miettinen TA, Gylling H, Lindbohm N, Miettinen TE, Rajaratnam RA, Relas H. Serum, noncholesterol sterols during inhibition of cholesterol synthesis by statins. J Lab Clin Med. 2003;141:131-137.
10. Pramfalk C, Davis MA, Eriksson M, Rudel LL, Parini P. Control of ACAT2 liver expression by HNFl. J Lipid Res. 2005;46:1868-1876.
11. Rudel LL, Lee RG, Cockman TL. Acyl coenzyme A: cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis. Curr Opin Lipidol. 2001;12:121-127.
12. Lee RG, Keliey KL, Sawyer JK, Farese RV Jr, Parks JS, Rudel LL. Plasma cholesteryl esters provided by lecithin:cholesterol acyltransferase and acyl-coenzyme a:cholesterol acyltransferase 2 have opposite atherosclerotic potential. Circ Res. 2004;95:998-1004.
13. Twisk J, Gillian-Daniel DL, Tebon A, Wang L, Barrett PHR, Attic AD. The role of the LDL receptor in apolipoprotein B secretion. J Clin Invest. 2000;105:521 532.
14. Reihnér E, Rudling M, Stâhlberg D, Berglund L, Ewerth S, Björkhem I, Einarsson K, Angelin B. Influence of pravastatin, a specific inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol. N Engl J Med. 1990;323:224.228.
15. Rudling MJ, Reihnér E, Einarsson K, Ewerth S, Angelin B. Low density lipoprotein receptor-binding activity in human tissues: quantitative importance of hepatic receptors and evidence for regulation of their expression in vivo. Proc Natl Acad Sci USA. 1990;87:3469-3473.
16. Rudling M, Angelin B, Stahle L, Reihnér E, Sahlin S, Olivecrona H, Björkhem I, Einarsson C. Regulation of hepatic low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and cholesterol 7alpha-hydroxylase mRNAs in human liver. J Clin Endocrinol Metab. 2002;87:4307 4313.
17. Nilsson LM, Abrahamsson A, Sahlin S, Gustafsson U, Angelin B, Parini. P, Einarsson C. Bile acids and lipoprotein metabolism: effects of cholestyramine and chenodeoxycholic acid on human hepatic mRNA expression. Biochem Biophys Res Commun. 2007;357:707-711.
18. Dubuc G, Chamberland A, Wassef H, Davignon J, Seidah NG, Bernier L. Prat A. Statins upregulate PCSK9, die gene encoding die proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vase Biol. 2004;24:1454-1459.
19. Kuipers F, Jong MC, Lin Y, Eck M, Havinga R, Bloks V, Verkade HJ, Hofker MH, Moshage H, Berkel TJ, Vonk RJ, Havekes LM. Impaired secretion of very low density lipoprotein-triglycerides by apolipoprotein E-deficient mouse hepatocytes. J Clin Invest. 1997; 100:2915-2922.
20. Maugeais C, Tietge UJ, Tsukamoto K, Glick JM, Rader DJ. Hepatic apolipoprotein E expression promotes very low density lipoproteinapolipoprotein B production in vivo in mice. J Lipid Res. 2000;41: 1673-1679.
21. Huang Y, Liu XQ, Rail SC Jr, Taylor JM., von Eckardstein A, Assmann G, Mahley RW. Overexpression and accumulation of apolipoprotein E as a cause of hypertriglyceridemia. J Biol Chem. 1998;273:26388. 26393.
22. Willner EL, Tow B, Buhman KK, Wilson M, Sanan DA, Rudel LL, Farese RV Jr. Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Proc Natl Acad Sci USA. 2003;100:1262-1267.
23. Rudel LL, Haines J, Sawyer JK, Shah R, Wilson MS, Carr TP. Hepatic origin of cholesteryl oleate in coronary artery atherosclerosis in African green monkeys: enrichment by dietary monounsaturated fat. J Clin Invest. 1997;100:74-83.
24. Mora S, Szklo M, Otvos JD, Greenland P, Psaty BM, Goff DC Jr, O'Leary DH, Saad MF, Tsai MY, Sharrett AR. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2007;192:211-217.
25. Rudel LL, Davis M, Sawyer J, Shah R, Wallace J. Primates highly responsive to dietary cholesterol up-regulate hepatic ACAT2, and less responsive primates do not. J Biol Chem. 2002;277:31401-31406.
26. Pramfalk C, Angelin B, Eriksson M, Parini. P. Cholesterol regulates ACAT2 gene expression and enzyme activity in human hepatoma cells. Biochem Biophys Res Commun. 2007;364:402-409.
27. Parini P, Johansson L, Bröijersén A, Angelin B, Rudling M. Lipoprotein profiles in plasma and interstitial fluid analyzed with an automated gel-filtration system. Eur J Clin Invest. 2006;36:98-104.
28. Timmins JM, Lee JY, Boudyguina E, Kluckman KD, Brunliam LR, Mulya A, Gebre AK, Coutinho JM, Colvin PL, Smith TL, Hayden MR, Maeda N, Parks JS. Targeted inactivation of hepatic Abcal causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I. J Clin Invest. 2005;115:1333-1342.
29. Mazzella G, Parini P, Festi D, Bazzoli F, Aldini R, Roda A, Tonelli D, Cipolla A, Salzetta A, Roda E. Effects of simvastatin, ursodeoxycholic acid and simvastatin plus ursodeoxycholic acid on biliary lipid secretion and cholic acid kinetics in nonfamilial hypercholesterolemia. Hepatology. 1992;15:1072-1078.
30. Yu L, Hammer RE, Li-Hawkins J, Von Bergmann K, Lutjohann D, Cohen JC, Hobbs HH. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci USA. 2002;99:16237-16242.
31. Postiglione A, Montefusco S, Pauciullo P, Mancini M, Piliego T. Effects of atorvastatin in patients with homozygous familial hypercholesterolemia. Atherosclerosis. 1999;147:423-424.