Predicting the risk of cardiovascular disease: where does lipoprotein-associated phospholipase A(2) fit in?
Although an atherogenic lipoprotein phenotype has been well recognized as an important predictor of cardiovascular disease, recent studies have demonstrated a number of additional lipid-related markers as emerging biomarkers to identify patients at risk for future coronary heart disease. Among them, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), seems to be a promising candidate that might be added to the clinical armamentarium for improved prediction of cardiovascular disease in the future. Of particular note, Lp-PLA(2) is the only enzyme that cleaves oxidized low-density lipoprotein (oxLDL) in the subendothelial space, with further generation of proinflammatory mediators such as lysophosphatidylcholine (LysoPC) and oxidized fatty acid (oxFA), thereby probably linking two important features of atherogenesis, namely oxidation of LDL and local inflammatory processes within the atherosclerotic plaque. This overview aims to summarize our current knowledge based on observations from recent experimental and clinical studies. Emphasis has been put on potential pathophysiological mechanisms of action and on the clinical relevance of Lp-PLA(2) in a wide variety of clinical settings, including apparently healthy individuals, patients with stable angina or acute coronary syndromes, after myocardial infarction, and with subclinical disease. Although a growing body of evidence from epidemiological and clinical studies suggests that Lp-PLA(2) may represent an independent and clinically relevant long-term risk marker for coronary heart disease and, probably, also for stroke, the role of this enzyme in the setting of the acute coronary syndrome remains to be established.
Khuseyinova
Natalie
N
Department of Internal Medicine II - Cardiology, University of Ulm Medical Center, Ulm, Germany.
Koenig
Wolfgang
W
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000201:enzymology* / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D015201:Meta-Analysis as Topic; D012307:Risk Factors
D002097:C-Reactive Protein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase
Atherosclerosis. 2005 Sep;182(1):181-8
16115490
Circulation. 2007 Feb 20;115(7):928-35
17309939
Angiology. 2005 Jul-Aug;56(4):451-8
16079929
Arterioscler Thromb Vasc Biol. 2002 Feb 1;22(2):306-11
11834533
Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):631-6
16373603
Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):216-21
15499045
Am J Cardiol. 1999 Jan 1;83(1):109-11, A8-9
10073795
Vasc Med. 2004 May;9(3):171-6
15675180
Clin Chem. 1997 Jan;43(1):52-8
8990222
Curr Drug Targets Cardiovasc Haematol Disord. 2005 Dec;5(6):527-32
16503872
Am J Epidemiol. 1999 Feb 1;149(3):261-7
9927222
Crit Care Med. 2004 Feb;32(2):332-41
14758145
Maturitas. 1999 Mar 15;31(3):249-53
10340285
Arch Intern Med. 2006 Jul 10;166(13):1368-73
16832001
Atherosclerosis. 2005 Sep;182(1):193-8
15982658
Nat Clin Pract Cardiovasc Med. 2005 Oct;2(10 ):529-35
16186851
N Engl J Med. 2000 Oct 19;343 (16):1148-55
11036120
Lipids. 1991 Dec;26(12 ):1015-20
1819685
FEBS Lett. 2001 Sep 21;505(3):357-63
11576528
Arterioscler Thromb Vasc Biol. 1999 Dec;19(12 ):2909-17
10591668
J Clin Invest. 1992 Sep;90(3):1138-44
1381720
Expert Rev Mol Diagn. 2005 Jan;5(1):9-14
15723587
Am Heart J. 2006 Nov;152(5):997-1003
17070179
Proc Natl Acad Sci U S A. 1988 Apr;85(8):2805-9
3357891
Clin Chim Acta. 1991 Oct 14;202(1-2):95-103
1807873
Mayo Clin Proc. 2007 Feb;82(2):159-65
17290721
Eur Heart J. 2007 Mar;28(6):699-704
17314110
Arch Intern Med. 2005 Nov 28;165(21):2479-84
16314544
Curr Opin Pharmacol. 2006 Apr;6(2):154-61
16495153
Clin Biochem. 2004 Mar;37(3):210-6
14972643
Bioorg Med Chem Lett. 2002 Sep 16;12 (18):2603-6
12182870
Circulation. 2004 Jun 29;109(25 Suppl 1):IV3-5
15226245
Circulation. 2005 Feb 8;111(5):570-5
15699277
J Biol Chem. 1997 Jul 18;272(29):17895-8
9218411
Am J Cardiol. 2005 May 1;95(9):1025-32
15842965
Arterioscler Thromb Vasc Biol. 2005 May;25(5):923-31
15731492
Circulation. 2004 Feb 24;109 (7):837-42
14757686
Clin Chem. 2001 Mar;47(3):444-50
11238295
Circulation. 2004 Oct 5;110(14 ):1903-8
15451783
J Am Coll Cardiol. 2006 Jul 18;48(2):396-401
16843192
J Biochem. 2002 May;131(5):635-40
11983068
Circulation. 2005 Mar 1;111(8):980-7
15710755
Am J Epidemiol. 2004 May 1;159(9):882-90
15105181
Arch Intern Med. 2006 Oct 23;166(19):2073-80
17060536
Clin Chem. 1989 May;35(5):783-6
2720971
J Am Coll Cardiol. 2001 Nov 1;38(5):1302-6
11691499
Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):106-11
16239595
Clin Chem. 2006 Jul;52(7):1331-8
16709622
Am J Cardiol. 2006 Mar 1;97(5):640-5
16490429
Lancet. 2001 Jun 16;357(9272):1915-24
11425411
Bioorg Med Chem Lett. 2003 Mar 24;13(6):1067-70
12643913
Circulation. 2003 Jan 28;107(3):499-511
12551878
Circulation. 2006 Apr 11;113(14 ):1745-52
16537575
J Lipid Res. 2003 Jul;44(7):1381-6
12730297
Atherosclerosis. 2000 Jun;150(2):413-9
10856534
Biochim Biophys Acta. 2000 Oct 31;1488(1-2):102-23
11080681
Eur J Cardiovasc Prev Rehabil. 2007 Feb;14(1):3-11
17301621
Mol Diagn Ther. 2007;11(4):219-26
17705576
Lancet. 1999 Aug 28;354(9180):708-15
10475181
Atherosclerosis. 2007 Apr;191(2):377-83
16678183
Am J Cardiol. 2002 Apr 1;89(7):860-1
11909576
Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2523-9
16960105
Clin Res Cardiol. 2007 Sep;96(9):604-12
17593313
Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1586-93
16627803
Biochem J. 1999 Mar 1;338 ( Pt 2):479-87
10024526
Farmaco. 2001 Jan-Feb;56(1-2):45-50
11347966
J Biol Chem. 1999 Mar 12;274(11):7018-24
10066756
Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2517-22
16902161
Biochem Biophys Res Commun. 1999 Aug 2;261(2):511-4
10425216
Eur Heart J. 2005 Jan;26(2):137-44
15618069
Nature. 1995 Apr 6;374(6522):549-53
7700381
Prev Cardiol. 2006 Summer;9(3):138-43
16849876
Am J Cardiol. 2005 May 15;95(10 ):1246-7
15878003
J Clin Endocrinol Metab. 2004 Mar;89(3):1153-9
15001601
Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):523-7
10934081
JAMA. 2007 Feb 14;297(6):611-9
17299196
J Lipid Res. 2003 May;44(5):927-34
12611907
Clin Chem. 2004 Nov;50(11):2077-82
15364890
Metabolism. 1993 Jun;42(6):672-7
8510509
Clin Chim Acta. 2001 Oct;312(1-2):179-83
11580924
Am J Cardiol. 2006 Sep 15;98 (6):743-5
16950175