Investigational Drugs Targeting HDL-C Metabolism And Reverse Cholesterol Transport

Bibliography

• 1. National Cholesterol Education Panel. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation 106, 3143–3421 (2002).
   Google Scholar
• US cholesterol guidelines.
   Google Scholar
• Gotto AM Jr, Whitney E, Stein EA et al.: Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 101, 477–484 (2000).
   Google Scholar
• Gordon D, Probstfield J, Garrison R et al.: High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation 79, 8–15 (1989).
   Google Scholar
• Describes the relationship between high-density lipoprotein cholesterol (HDL-C) and cardiovascular risk.
   Google Scholar
• Lewis G, Rader D: New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ. Res. 96, 1221–1232 (2005).
   Google Scholar
• Review of HDL metabolism.
   Google Scholar
• Barter PJ, Nicholls S, Rye K-A, Anantharamaiah GM, Navab M, Fogelman AM: Anti-inflammatory properties of HDL. Circ. Res. 95, 764–772 (2004).
   Google Scholar
• Review of the anti-inflammatory properties of HDL.
   Google Scholar
• Mineo C, Deguchi H, Griffin JH, Shaul PW: Endothelial and antithrombotic actions of HDL. Circ. Res. 98, 1352–1364 (2006).
   Google Scholar
• Review of the endothelial antithrombotic activities of HDL.
   Google Scholar
• Tall AR, Yvan-Charvet L, Wang N: The failure of torcetrapib: was it the molecule or the mechanism? Arterioscler. Thromb. Vasc. Biol. 27, 257–260 (2007).
   Google Scholar
• Report on the early termination of the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial and potential reasons why.
   Google Scholar
• Yancey PG, Bortnick AE, Kellner-Weibel G, de la Llera-Moya M, Phillips MC, Rothblat GH: Importance of different pathways of cellular cholesterol efflux. Arterioscler. Thromb. Vasc. Biol. 23, 712–719 (2003).
   Google Scholar
• Review of reverse cholesterol transport.
   Google Scholar
• O’Brien KD, McDonald TO, Kunjathoor V et al.: Serum amyloid A and lipoprotein retention in murine models of atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 25, 785–790 (2005).
   Google Scholar
• Massamiri T, Tobias PS, Curtiss LK: Structural determinants for the interaction of lipopolysaccharide binding protein with purified high density lipoproteins: role of apolipoprotein A-I. J. Lipid Res. 38, 516–525 (1997).
   Google Scholar
• Pownall HCE: The unique role of apolipoprotein A-I in HDL remodeling and metabolism. Curr. Opin. Lipidol. 17, 209–213 (2006).
   Google Scholar
• Review of apolipoprotein (apo)A-I.
   Google Scholar
• Ory DS: Nuclear receptor signaling in the control of cholesterol homeostasis: have the orphans found a home? Circ. Res. 95, 660–670 (2004).
   Google Scholar
• Review of the nuclear receptors liver X receptor (LXR) and farnesoid X receptor (FXR).
   Google Scholar
• Zelcer N, Tontonoz P: Liver X receptors as integrators of metabolic and inflammatory signaling. J. Clin. Invest. 116, 607–614 (2006).
   Google Scholar
• Review of LXR.
   Google Scholar
• Wang N, Lan D, Chen W, Matsuura F, Tall AR: ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc. Natl Acad. Sci. USA 101, 9774–9779 (2004).
   Google Scholar
• Oram JF, Vaughan AM: ATP-binding cassette cholesterol transporters and cardiovascular disease. Circ. Res. 99, 1031–1043 (2006).
   Google Scholar
• Review of ATP-binding cassette transporters.
   Google Scholar
• Schmitz G, Langmann T: High-density lipoproteins and ATP-binding cassette transporters as targets for cardiovascular drug therapy. Curr. Opin. Investig. Drugs 6, 907–919 (2005).
   Google Scholar
• Joyce CW, Wagner EM, Basso F et al.: ABCA1 overexpression in the liver of LDLr-KO mice leads to accumulation of p-atherogenic lipoproteins and enhanced atherosclerosis. J. Biol. Chem. 281, 33053–33065 (2006).
   Google Scholar
• Out R, Hoekstra M, Meurs I et al.: Total body ABCG1 expression protects against early atherosclerotic lesion development in mice. Arterioscler. Thromb. Vasc. Biol. 27, 594–599 (2007).
   Google Scholar
• Basso F, Amar MJ, Wagner EM et al.: Enhanced ABCG1 expression increases atherosclerosis in LDLr-KO mice on a western diet. Biochem. Biophys. Res. Commun. 351, 398–404 (2006).
   Google Scholar
• Wang J, Einarsson C, Murphy C et al.: Studies on LXR- and FXR-mediated effects on cholesterol homeostasis in normal and cholic acid-depleted mice. J. Lipid Res. 47, 421–430 (2006).
   Google Scholar
• Claudel T, Staels B, Kuipers F: The farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler. Thromb. Vasc. Biol. 25, 2020–2030 (2005).
   Google Scholar
• Review of FXR.
   Google Scholar
• Watanabe M, Houten SM, Wang L et al.: Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J. Clin. Invest. 113, 1408–1418 (2004).
   Google Scholar
• Jansen H: Hepatic lipase: friend or foe and under what circumstances? Curr. Atheroscler. Rep. 6, 343–347 (2004).
   Google Scholar
• Review of hepatic lipase.
   Google Scholar
• Rashid S, Watanabe T, Sakaue T, Lewis G: Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase acivity. Clin. Biochem. 36, 421–429 (2003).
   Google Scholar
• Badellino K, Wolfe M, Reilly M, Rader D: Endothelial lipase concentrations are increased in metabolic syndrome and associated with coronary atherosclerosis. PLoS Med. 3, E22 (2005).
   Google Scholar
• Duffy D, Rader DJ: Emerging therapies targeting high-density lipoprotein metabolism and reverse cholesterol transport. Circulation 113, 1140–1150 (2006).
   Google Scholar
• Review of drugs targeting HDL-C.
   Google Scholar
• Ishida T, Choi SY, Kundu RK et al.: Endothelial lipase modulates susceptibility to atherosclerosis in apolipoprotein E-deficient mice. J. Biol. Chem. 279, 45085–45092 (2004).
   Google Scholar
• Jin W, Marchadier D, Rader DJ: Lipases and HDL metabolism. Trends Endocrinol. Metab. 3, 174–178 (2002).
   Google Scholar
• Review of hepatic and endothelial lipases.
   Google Scholar
• Rothblat GH, de la Llera-Moya M, Atger V, Kellner-Weibel G, Williams DL, Phillips MC: Cell cholesterol efflux: integration of old and new observations provides new insights. J. Lipid Res. 40, 781–796 (1999).
   Google Scholar
• Zhang S, Picard MH, Vasile E et al.: Diet-induced occlusive coronary atherosclerosis, myocardial infarction, cardiac dysfunction, and premature death in scavenger receptor class b type I-deficient, hypomorphic apolipoprotein ER61 mice. Circulation 111(2), 3457–3464 (2005).
   Google Scholar
• Tall AR, Jiang X-C, Luo Y, Silver D: 1999 George Lyman Duff Memorial Lecture: lipid transfer proteins, HDL metabolism, and atherogenesis. Arterioscler. Thromb. Vasc. Biol. 20, 1185–1188 (2000).
   Google Scholar
• Offermanns S: The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target. Trends Pharmacol. Sci. 27, 384–390 (2006).
   Google Scholar
• Review of mechanisms for niacin.
   Google Scholar
• Heeren J, Beisiegel U, Grewal T: Apolipoprotein E recycling: implications for dyslipidemia and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 26, 442–448 (2006).
   Google Scholar
• Barter PJ, Kastelein JJP: Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J. Am. Coll. Cardiol. 47, 492–499 2006).
   Google Scholar
• Review of cholesteryl ester transfer protein (CETP) inhibition prior to the ILLUMINATE trial.
   Google Scholar
• Boekholdt SM, Sacks FM, Jukema JW et al.: Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation 111, 278–287 (2005).
   Google Scholar
• Meta-analysis of TaqIB and cardiovascular risk.
   Google Scholar
• Barzilai N, Atzmon G, Schechter C et al.: Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 290, 2030–2040 (2003).
   Google Scholar
• Hirano K, Yamashita S, Kuga Y et al.: Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase. Arterioscler. Thromb. Vasc. Biol. 15, 1849–1856 (1995).
   Google Scholar
• Zhong S, Sharp DS, Grove JS et al.: Increased coronary heart disease in Japanese–American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels. J. Clin. Invest. 97, 2917–2923 (1996).
   Google Scholar
• Curb JD, Abbott RD, Rodriguez BL et al.: A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly. J. Lipid Res. 45, 948–953 (2004).
   Google Scholar
• Huuskonen J, Olkkonen VM, Jauhiainen M, Ehnholm C: The impact of phospholipid transfer protein (PLTP) on HDL metabolism. Atherosclerosis 155, 269–281 (2001).
   Google Scholar
• Review of phospholipid transfer protein.
   Google Scholar
• Jiang X-C, Bruce C, Mar J et al.: Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels. J. Clin. Invest. 103, 907–914 (1999).
   Google Scholar
• Liu R, Hojjati MR, Devlin CM, Hansen IH, Jiang XC: Macrophage phospholipid transfer protein deficiency and apoE secretion. Impact on mouse plasma cholesterol levels and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 27(1), 190–196 (2007).
   Google Scholar
• Tan K, Shiu S, Wong Y, Tam S: Plasma phospholipid transfer protein activity and subclinical inflammation in Type 2 diabetes mellitus. Atherosclerosis 178, 365–370 (2005).
   Google Scholar
• Schlitt A, Liu J, Yan D, Mondragon-Escorpizo M, Norin AJ, Jiang X-C: Anti-inflammatory effects of phospholipid transfer protein (PLTP) deficiency in mice. Biochim. Biophys. Acta 1733, 187–191 (2005).
   Google Scholar
• Grundy SM: Hypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome. Am. J. Cardiol. 81(4 Suppl. 1), 18B–25B (1998).
   Google Scholar
• Horowitz B, Goldberg I, Merab J, Vanni T, Ramakrishnan R, Ginsberg H: Increased plasma and renal clearance of an exchangeable pool of apolipoprotein A-I in subjects with low levels of high density lipoprotein cholesterol. J. Clin. Invest. 91, 1743–1752 (1993).
   Google Scholar
• Hansel B, Giral P, Nobecourt E et al.: Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. J. Clin. Endocrinol. Metab. 89, 4963–4971 (2004).
   Google Scholar
• Kontush A, Chapman M: Antiatherogenic small, dense HDL – guardian angel of the arterial wall? Nat. Clin. Pract. Cardiovasc. Med. 3, 144–153 (2006).
   Google Scholar
• Review of HDL size.
   Google Scholar
• Niu N, Zhu X, Liu Y et al.: Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein M gene (apoM) confer the susceptibility to development of Type 2 diabetes in Han Chinese. Diabetes Metab. Res. Rev. 23, 21–25 (2007).
   Google Scholar
• Dahlback B, Nielsen L: Apolipoprotein M – a novel player in high-density lipoprotein metabolism and atherosclerosis. Curr. Opin. Lipidol. 17, 291–295 (2006).
   Google Scholar
• Review of apoM.
   Google Scholar
• Sirtori C, Calabresi L, Franceschini G et al.: Cardiovascular status of carriers of the apolipoprotein A-I (Milano) mutant: the Limone sul Garda study. Circulation 103, 1949–1954 (2001).
   Google Scholar
• Calabresi L, Sirtori CR, Paoletti R, Franceschini G: Recombinant apolipoprotein A-I Milano for the treatment of cardiovascular events. Curr. Atheroscler. Rep. 8, 163–167 (2006).
   Google Scholar
• Review of apoA-I Milano.
   Google Scholar
• Bielicki J, Oda M: Apolipoprotein A-I(Milano) and apolipoprotein A-I(Paris) exhibit an antioxidant activity distinct from that of wild-type apolipoprotein A-I. Biochemistry 41, 2089–2096 (2002).
   Google Scholar
• Calabresi L, Tedeschi G, Treu C et al.: Limited proteolysis of a disulfide-linked apoA-I dimer in reconstituted HDL. J. Lipid Res. 242, 935–942 (2001).
   Google Scholar
• Nissen SE, Tsunoda T, Tuzcu EM et al.: Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 290, 2292–2300 (2003).
   Google Scholar
• Wang L, Sharifi BG, Pan T, Song L, Yukht A, Shah PK: Bone marrow transplantation shows superior atheroprotective effects of gene therapy with apolipoprotein A-I Milano compared with wild-type apolipoprotein A-I in hyperlipidemic mice. J. Am. Coll. Cardiol. 48, 1459–1468 (2006).
   Google Scholar
• Daum U, Langer C, Duverger N et al.: Apolipoprotein A-I(R151C)Paris is defective in activation of lecithin:cholesterol acyltransferase but not in initial lipid binding, formation of reconstituted lipoproteins, or promotion of cholesterol efflux. J. Mol. Med. 77, 614–622 (1999).
   Google Scholar
• Jia Z, Natarajan P, Forte TM, Bielicki JK: Thiol-bearing synthetic peptides retain the antioxidant activity of apolipoprotein A-IMilano. Biochem. Biophys. Res. Commun. 297, 206–213 (2002).
   Google Scholar
• Sacks FM, Brewer HB, Alaupovic P et al.: Selective plasma HDL delipidation and reinfusion: a unique approach for acute HD: therapy in the treatment of cardiovascular disease. Presented at: American Heart Association Scientific Sessions. New Orleans, LA, USA, 7–10 November 2004.
   Google Scholar
• Datta G, Chaddha M, Hama S et al.: Effects of increasing hydophobicity on the physical–chemical and biological properties of a class A amphipathic helical peptide. J. Lipid Res. 42, 1096–1104 (2001).
   Google Scholar
• Navab M, Anantharamaiah GM, Hama S et al.: Oral administration of an apo A-I mimetic peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol. Circulation 105, 290–292 (2002).
   Google Scholar
• Navab M, Anantharamaiah GM, Reddy ST et al.: Oral D-4F causes formation of pre- high-density lipoprotein and improves high-density lipoprotein-mediated cholesterol efflux and reverse cholesterol transport from macrophages in apolipoprotein E-null mice. Circulation 109(25), 3215–3220 (2004).
   Google Scholar
• Van Lenten BJ, Wagner AC, Anantharamaiah GM et al.: Influenza infection promotes macrophage traffic into arteries of mice that is prevented by D-4F, an apolipoprotein A-I mimetic peptide. Circulation 106, 1127–1132 (2002).
   Google Scholar
• Ou J, Ou Z, Jones DW et al.: L-4F, an apolipoprotein A-1 mimetic, dramatically improves vasodilation in hypercholesterolemia and sickle cell disease. Circulation 107, 2337–2341 (2003).
   Google Scholar
• Ou Z, Ou J, Ackerman AW, Oldham KT, Pritchard KA Jr: L-4F, an apolipoprotein A-1 mimetic, restores nitric oxide and superoxide anion balance in low-density lipoprotein-treated endothelial cells. Circulation 107, 1520–1524 (2003).
   Google Scholar
• Remaley A, Thomas F, Stonik J et al.: Synthetic amphipathic helical peptides promote lipid efflux from cells by an ABCA1-dependent and an ABCA1- independent pathway. J. Lipid Res. 44, 828–836 (2003).
   Google Scholar
• Gupta H, White CR, Handattu S et al.: Apolipoprotein E mimetic peptide dramatically lowers plasma cholesterol and restores endothelial function in Watanabe heritable hyperlipidemic rabbits. Circulation 111, 3112–3118 (2005).
   Google Scholar
• Davidson MH, McKenney JM, Shear CL, Revkin JH: Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with belowaverage high-density lipoprotein cholesterol levels. J. Am. Coll. Cardiol. 48, 1774–1781 (2006).
   Google Scholar
• McKenney JM, Davidson MH, Shear CL, Revkin JH: Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with belowaverage high-density lipoprotein cholesterol levels on a background of atorvastatin. J. Am. Coll. Cardiol. 48, 1782–1790 (2006).
   Google Scholar
• Clark RW, Ruggeri RB, Cunningham D, Bamberger MJ: Description of the torcetrapib series of cholesteryl ester transfer protein inhibitors, including mechanism of action. J. Lipid Res. 47, 537–552 (2006).
   Google Scholar
• Review of CETP inhibition prior to the ILLUMINATE trial.
   Google Scholar
• Brousseau ME, Diffenderfer MR, Millar JS et al.: Effects of cholesteryl ester transfer protein inhibition on high-density lipoprotein subspecies, apolipoprotein A-I metabolism, and fecal sterol excretion. Arterioscler. Thromb. Vasc. Biol. 25, 1057–1064 (2005).
   Google Scholar
• Lloyd DB, Lira ME, Wood LS et al.: Cholesteryl ester transfer protein variants have differential stability but uniform inhibition by torcetrapib. J. Biol. Chem. 280, 14918–14922 (2005).
   Google Scholar
• Morehouse L, Sugarman E, Bourassa P, Milici A: The CETP-inhibitor torcetrapib raises HDL and prevents aortic atherosclerosis in rabbits. Presented at: XV International Symposium on Drugs Affecting Lipid Metabolism. Venice, Italy, 24–27 October 2004.
   Google Scholar
• Brousseau ME, Schaefer EJ, Wolfe ML et al.: Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N. Engl. J. Med. 350, 1505–1515 (2004).
   Google Scholar
• Clark RW, Sutfin TA, Ruggeri RB et al.: Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapib. Arterioscler. Thromb. Vasc. Biol. 24, 490–497 (2004).
   Google Scholar
• Matsuura F, Wang N, Chen W, Jiang X-C, Tall AR: HDL from CETP-deficient subjects shows enhanced ability to promote cholesterol efflux from macrophages in an apoE- and ABCG1-dependent pathway. J. Clin. Invest. 116(5), 1435–1442 (2006).
   Google Scholar
• Ishigami M, Yamashita S, Sakai N et al.: Large and cholesteryl ester-rich high-density lipoproteins in cholesteryl ester transfer protein (CETP) deficiency can not protect macrophages from cholesterol accumulation induced by acetylated low-density lipoproteins. J. Biochem. 116, 257–262 (1994).
   Google Scholar
• Ohta T, Nakamura R, Takata K et al.: Structural and functional differences of subspecies of apoA-I- containing lipoprotein in patients with plasma cholesteryl ester transfer protein deficiency. J. Lipid Res. 36, 696–704 (1995).
   Google Scholar
• Millar JS, Brousseau ME, Diffenderfer MR et al.: Effects of the cholesteryl ester transfer protein inhibitor torcetrapib on apolipoprotein B100 metabolism in humans. Arterioscler. Thromb. Vasc. Biol. 26, 1350–1356 (2006).
   Google Scholar
• Okamoto H, Yonemori F, Wakitani K et al.: A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature 406, 203–207 (2000).
   Google Scholar
• de Grooth GJ, Kuivenhoven JA, Stalenhoef AFH et al.: Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized Phase II dose-response study. Circulation 105, 2159–2165 (2002).
   Google Scholar
• Kuivenhoven J, de Grooth G, Kawamura H et al.: Effectiveness of inhibition of cholesteryl ester transfer protein by JTT-705 in combination with pravastatin in type II dyslipidemia. Am. J. Cardiol. 95, 1085–1088 (2005).
   Google Scholar
• Ryan US, Rittershaus CW: Vaccines for the prevention of cardiovascular disease. Vasc. Pharmacol. 45, 253–257 (2006).
   Google Scholar
• Review of HDL vaccines.
   Google Scholar
• Rittershaus CW, Miller DP, Thomas LJ et al.: Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 20, 2106–2112 (2000).
   Google Scholar
• Rodrigueza WV, Klimuk SK, Pritchard PH, Hope MJ: Cholesterol mobilization and regression of atheroma in cholesterol-fed rabbits induced by large unilamellar vesicles. Biochim. Biophys. Acta 1368, 306–320 (1998).
   Google Scholar
• Navab M, Hama S, Hough G, Fogelman AM: Oral synthetic phospholipid (DMPC) raises high-density lipoprotein cholesterol levels, improves high-density lipoprotein function, and markedly reduces atherosclerosis in apolipoprotein E-null mice. Circulation 108, 1735–1739 (2003).
   Google Scholar
• Burgess JW, Neville TAM, Rouillard P, Harder Z, Beanlands DS, Sparks DL: Phosphatidylinositol increases HDL-C levels in humans. J. Lipid Res. 46, 350–355 (2005).
   Google Scholar
• de Vries R, Dallinga-Thie GM, Smit AJ, Wolffenbuttel BHR, van Tol A, Dullaart RPF: Elevated plasma phospholipid transfer protein activity is a determinant of carotid intima-media thickness in Type 2 diabetes mellitus. Diabetologia 49, 398–404 (2006).
   Google Scholar
• Li AC, Glass CK: PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis. J. Lipid Res. 45, 2161–2173 (2004).
   Google Scholar
• Miao B, Zondlo S, Gibbs S et al.: Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator. J. Lipid Res. 45, 1410–1417 (2004).
   Google Scholar
• Naik SU, Wang X, Da Silva JS et al.: Pharmacological activation of liver X receptors promotes reverse cholesterol transport in vivo. Circulation 113(1), 90–97 (2006).
   Google Scholar
• Brunham LR, Kruit JK, Pape TD, Parks JS, Kuipers F, Hayden MR: Tissue-specific induction of intestinal ABCA1 expression with a liver X receptor agonist raises plasma HDL cholesterol levels. Circ. Res. 99, 672–674 (2006).
   Google Scholar
• Ulbricht C, Basch E, Szapary P et al.: Guggul for hyperlipidemia: a review by the Natural Standard Research Collaboration. Complement. Ther. Med. 13, 279–290 (2005).
   Google Scholar
• Szapary PO, Wolfe ML, Bloedon LT et al.: Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 290, 765–772 (2003).
   Google Scholar
• Evans R, Barish G, Wang Y-X: PPARs and the complex journey to obesity. Nat. Med. 10, 1–7 (2004).
   Google Scholar
• Lefebvre P, Chinetti G, Fruchart J-C, Staels B: Sorting out the roles of PPAR in energy metabolism and vascular homeostasis. J. Clin. Invest. 116, 571–580 (2006).
   Google Scholar
• Review of peroxisome proliferatoractivated receptor (PPAR)α mechanisms of action.
   Google Scholar
• Guerin M, Bruckert E, Dolphin PJ, Turpin G, Chapman MJ: Fenofibrate reduces plasma cholesteryl ester transfer from HDL to VLDL and normalizes the atherogenic, dense LDL profile in combined hyperlipidemia. Arterioscler. Thromb. Vasc. Biol. 16, 763–772 (1996).
   Google Scholar
• Birjmohun RS, Hutten BA, Kastelein JJP, Stroes ESG. Efficacy and safety of high-density lipoprotein cholesterolincreasing compounds: a meta-analysis of randomized controlled trials. J. Am. Coll. Cardiol. 45, 185–197 (2005).
   Google Scholar
• Meta-analysis of fibrate and niacin randomized controlled trials.
   Google Scholar
• Committee of Principal Investigators: A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. Br. Heart J. 40, 1069–1118 (1978).
   Google Scholar
• Coronary Drug Project: Clofibrate and niacin in coronary heart disease. JAMA 231, 360–380 (1975).
   Google Scholar
• Tenkanen L, Manttari M, Manninen V: Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil: Experience from the Helsinki Heart Study. Circulation 92, 1779–1785 (1995).
   Google Scholar
• Rubins HB, Robins SJ, Collins D et al. : Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). Arch. Intern. Med. 162, 2597–2604 (2002).
   Google Scholar
• Tenenbaum A, Motro M, Fisman EZ, Tanne D, Boyko V, Behar S: Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch. Intern. Med. 165, 1154–1160 (2005).
   Google Scholar
• The FIELD study investigators: Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with Type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366, 1849–1861 (2005).
   Google Scholar
• Robins SJ, Collins D, Wittes JT et al.: Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 285, 1585–1591 (2001).
   Google Scholar
• Semple RK, Chatterjee VKK, O’Rahilly S: PPAR and human metabolic disease. J. Clin. Invest. 116(3), 581–589 (2006).
   Google Scholar
• Review of PPARα mechanisms of action.
   Google Scholar
• Dormandy J, Charbonnel B, Eckland D, et al.: Secondary prevention of macrovascular events in patients with Type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366, 1279–1289 (2005).
   Google Scholar
• Goldberg RB, Kendall DM, Deeg MA et al.: A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with Type 2 diabetes and dyslipidemia. Diabetes Care 28, 1547–1554 (2005).
   Google Scholar
• Mazzone T, Meyer PM, Feinstein SB et al.: Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in Type 2 diabetes: a randomized trial. JAMA 296, 2572–2525 (2006).
   Google Scholar
• The Dream Trial Investigators: Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 368, 1096–1105 (2006).
   Google Scholar
• Nissen SE, Wolski K, Topol EJ: Effect of muraglitazar on death and major adverse cardiovascular events in patients with Type 2 diabetes mellitus. JAMA 294, 2581–2586 (2005).
   Google Scholar
• Fagerberg B, Edwards S, Halmos T et al.: Tesaglitazar, a novel dual peroxisome proliferator-activated receptor α/γ agonist, dose-dependently improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population. Diabetologia 48, 1716–1725 (2005).
   Google Scholar
• Barish GD, Narkar VA, Evans RM: PPARδ: a dagger in the heart of the metabolic syndrome. J. Clin. Invest. 116, 590–597 (2006).
   Google Scholar
• Review of PPAR β/δ mechanisms of action.
   Google Scholar
• Wang Y-X: Peroxisome-proliferatoractivated receptor activated fat metabolism to prevent obesity Cell 113, 159–170 (2003).
   Google Scholar
• Sprecher DL, Massien C, Pearce G et al.: Triglyceride: high-density lipoprotein cholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor- agonist. Arterioscler. Thromb. Vasc. Biol. 27, 359–365 (2007).
   Google Scholar
• McKenney J: New perspectives on the use of niacin in the treatment of lipid disorders. Arch. Intern. Med. 164, 697–705 (2004).
   Google Scholar
• Review of niacin therapy.
   Google Scholar
• Karpe F, Frayn K: The nicotinic acid receptor – a new mechanism for an old drug. Lancet 363, 1892–1894 (2004).
   Google Scholar
• Niacin mechanism review.
   Google Scholar
• Rubic T, Trottmann M, Lorenz R: Stimulation of CD36 and the key effector of reverse choelsterol transport ATP-binding cassette A1 in monocytoid cells by niacin. Biochem. Pharmacol. 67, 411–419 (2004).
   Google Scholar
• Cheng K, Wu T-J, Wu KK et al.: Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. Proc. Natl Acad. Sci. USA 103, 6682–6687 (2006).
   Google Scholar
• McGovern M: Use of nicotinic acid in patients with elevated fasting glucose, diabetes, or metabolic syndrome. Br. J. Diabetes Vasc. Dis. 4, 78–85 (2004).
   Google Scholar
• Canner PL, Furberg CD, McGovern ME: Benefits of niacin in patients with versus without the metabolic syndrome and healed myocardial infarction (from the Coronary Drug Project). Am. J. Cardiol. 97, 477–479 (2006).
   Google Scholar
• Pfeffer MA, Sacks FM, Moye LA et al.: Influence of baseline lipids on effectiveness of pravastatin in the CARE trial. J. Am. Coll. Cardiol. 33, 125–130 (1999).
   Google Scholar
• Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360, 7–22 (2002).
   Google Scholar
• The Long-term Intervention with Pravastatin in Ischemic Disease Study: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N. Engl. J. Med. 339, 1349–1357 (1998).
   Google Scholar
• Shepherd J, Blauw G, Murphy M et al.: Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360, 1623–1630 (2002).
   Google Scholar