title: Raising high-density lipoprotein cholesterol: innovative strategies against an old adversary.
abstract: The lipid hypothesis, which was proposed over 100 years ago, is based on the premise that dyslipidemia is central to the process of atherosclerosis. Low-density lipoprotein and lipoprotein(a) are clearly atherogenic, whereas the role of very low-density lipoprotein as an independent factor is controversial. The only lipoprotein that is clearly antiatherogenic is high-density lipoprotein (HDL), which is thought to reduce coronary risk by mediating cholesterol efflux from the periphery by way of transportation to the liver for excretion. Traditionally, fibric acid derivatives and nicotinic acid were the major pharmacologic agents used to raise circulating levels of HDL. Recent therapeutic advances have been made in the ability to increase HDL. Apolipoprotein A-I Milano and cholesterol ester transfer protein represent novel approaches to the pharmacologic therapy of individuals with low HDL levels. The mechanisms and clinical implications of these interventions are discussed here.
authors.affiliation: Department of Internal Medicine, Baylor College of Medicine, One Baylor Plaza, MS 523D, Houston, TX 77030, USA.
authors.forename: Dhruv
authors.initials: D
authors.lastname: Kazi
authors.forename: John A
authors.initials: JA
authors.lastname: Farmer
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D008099:Liver / Q000378:metabolism; D009154:Mutation; D011379:Prognosis; D012307:Risk Factors
chemical_list: D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D015415:Biomarkers; D008076:Cholesterol, HDL
references.citation: Circulation. 2003 May 27;107(20):2551-4
references.pmid: 12742990
references.citation: J Biol Chem. 1982 Jun 25;257(12):6653-5
references.pmid: 7045092
references.citation: N Engl J Med. 1990 Nov 1;323(18):1234-8
references.pmid: 2215607
references.citation: Am J Cardiol. 2001 Dec 20;88(12A):9N-13N
references.pmid: 11788124
references.citation: J Investig Med. 1999 Jan;47(1):31-42
references.pmid: 10071479
references.citation: J Am Coll Cardiol. 2004 Mar 3;43(5):717-24
references.pmid: 14998606
references.citation: Nature. 2000 Jul 13;406(6792):203-7
references.pmid: 10910363
references.citation: Circulation. 2004 Sep 14;110(11):1418-23
references.pmid: 15337694
references.citation: Atherosclerosis. 1985 Dec;58(1-3):159-74
references.pmid: 3937534
references.citation: J Clin Invest. 1991 Jan;87(1):331-46
references.pmid: 1985105
references.citation: Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):2106-12
references.pmid: 10978256
references.citation: Arterioscler Thromb Vasc Biol. 1999 May;19(5):1257-62
references.pmid: 10323777
references.citation: Circulation. 2001 Jun 26;103(25):3047-50
references.pmid: 11425766
references.citation: J Lipid Res. 1985 Mar;26(3):273-82
references.pmid: 3989387
references.citation: Metabolism. 1975 Nov;24(11):1243-65
references.pmid: 171539
references.citation: N Engl J Med. 2004 Jun 10;350(24):2438-40
references.pmid: 15190135
references.citation: Circulation. 2002 May 7;105(18):2159-65
references.pmid: 11994249
references.citation: Chem Rev. 2004 Jan;104(1):119-37
references.pmid: 14719972
references.citation: J Lipid Res. 1991 Jun;32(6):917-33
references.pmid: 1940624
references.citation: J Clin Invest. 1991 Dec;88(6):2039-46
references.pmid: 1752961
references.citation: Nat Med. 2001 Jul;7(7):853-7
references.pmid: 11433352
references.citation: Proc Natl Acad Sci U S A. 2004 May 4;101(18):6999-7004
references.pmid: 15107497
references.citation: Science. 1996 Jan 26;271(5248):518-20
references.pmid: 8560269
references.citation: J Biol Chem. 1998 Feb 27;273(9):5033-6
references.pmid: 9478952
references.citation: Circ Res. 2002 May 17;90(9):974-80
references.pmid: 12016263
references.citation: J Clin Invest. 1980 Nov;66(5):892-900
references.pmid: 7430351
references.citation: Arterioscler Thromb Vasc Biol. 1998 Jun;18(6):861-9
references.pmid: 9633924
references.citation: Am J Cardiol. 1992 Dec 14;70(19):10H-13H
references.pmid: 1466311
references.citation: Atherosclerosis. 1994 Sep 30;110(1):101-9
references.pmid: 7857364
references.citation: Circulation. 1989 Jan;79(1):8-15
references.pmid: 2642759
references.citation: J Lipid Res. 1993 Aug;34(8):1255-74
references.pmid: 8409761
references.citation: Biochem J. 1996 Jan 1;313 ( Pt 1):275-82
references.pmid: 8546695
references.citation: Am J Hum Genet. 1985 Nov;37(6):1083-97
references.pmid: 3936350
references.citation: Atherosclerosis. 1999 Aug;145(2):227-38
references.pmid: 10488948
references.citation: J Biol Chem. 2001 Jul 6;276(27):25287-93
references.pmid: 11301333
references.citation: Nature. 1989 Nov 23;342(6248):448-51
references.pmid: 2586614
references.citation: J Clin Invest. 1989 Jul;84(1):129-37
references.pmid: 2738149
references.citation: J Lipid Res. 1991 Mar;32(3):439-47
references.pmid: 1906086
references.citation: Proc Natl Acad Sci U S A. 1978 Sep;75(9):4519-23
references.pmid: 212757
references.citation: Circulation. 1997 Jan 7;95(1):69-75
references.pmid: 8994419
references.citation: J Biol Chem. 1983 Feb 25;258(4):2508-13
references.pmid: 6401735
references.citation: JAMA. 2003 Nov 5;290(17 ):2292-300
references.pmid: 14600188
references.citation: Atherosclerosis. 1997 Jan 3;128(1):59-66
references.pmid: 9051198
references.citation: Biochemistry. 2002 Feb 12;41(6):2089-96
references.pmid: 11827556
references.citation: J Mol Med (Berl). 2001 May;79(4):161-7
references.pmid: 11409706
references.citation: Atherosclerosis. 2002 Mar;161(1):1-16
references.pmid: 11882312
references.citation: Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):160-7
references.pmid: 12588754
references.citation: J Biol Chem. 1997 Aug 22;272(34):20982-5
references.pmid: 9261096
references.citation: Am J Cardiol. 1991 Jun 1;67(15):1185-9
references.pmid: 2035438
references.citation: Can J Cardiol. 1988 Jul;4 Suppl A:5A-10A
references.pmid: 3179802
references.citation: N Engl J Med. 2004 Apr 8;350(15):1505-15
references.pmid: 15071125
references.citation: Atherosclerosis. 1985 Dec;58(1-3):175-86
references.pmid: 3937535