On the role of sPLA2 in atherosclerosis

sPLA2 genes are genetically associated with cardiovascular diseases in human

Genetic Variants within the PLA2G2A Gene Encoding Secretory Phospholipase A2 Group IIA are Related to the Risk of Myocardial InfarctionCirculation. Fischer Marcus; Andrea Baessler; Martina Koehler; Klaus Stark; Katharina Neureuther; Silke Wiedmann; Wibke Hengstenberg; Angela Doering; Heribert Schunkert; Guenter Riegger; Christian Hengstenberg. 2006;114: II_887.

Tagging SNP haplotype analysis of the secretory PLA2-V gene, PLA2G5, shows strong association with LDL and oxLDL levels, suggesting functional distinction from sPLA2-IIA: results from the UDACS study. Wootton PT, Arora NL, Drenos F, Thompson SR, Cooper JA, Stephens JW, Hurel SJ, Hurt-Camejo E, Wiklund O, Humphries SE, Talmud PJ. Hum Mol Genet. 2007 Jun 15;16(12):1437-44.

Influence of Variations of secretory PLA2-IIA gene on sPLA2 activity and one-year clinical outcome in patients with AMI. Results from FAST-MI registry. Simon T, Danchin N, Kotti-Tounsi S, Benessiano J, Lambeau G, Verstuyft C, Steg G, Bonnet PH, Tedgui A, Mallat Z. Presented at: European Society of Cardiology Meeting. Barcelona, Spain, 29 August-3 September 2009.

sPLA2 proteins are present in human atherosclerotic lesions and the extent of sPLA2 expression increased with atherosclerosis development (Kimura-Matsumoto M. et al., 2008)

Expression of secretory phospholipase A2s in human atherosclerosis development.Kimura-Matsumoto M, Ishikawa Y, Komiyama K, Tsuruta T, Murakami M, Masuda S, Akasaka Y, Ito K, Ishiguro S, Morita H, Sato S, Ishii T. Atherosclerosis. 2008 Jan;196(1):81-91. Epub 2007 Mar 13.

Transgenic mice overexpressing sPLA2 genes spontaneously develop atherosclerotic lesions

Role of group II secretory phospholipase A2 in atherosclerosis: 1. Increased atherogenesis and altered lipoproteins in transgenic mice expressing group IIa phospholipase A2. Ivandic B, Castellani LW, Wang XP, Qiao JH, Mehrabian M, Navab M, Fogelman AM, Grass DS, Swanson ME, de Beer MC, de Beer F, Lusis AJ. Arterioscler Thromb Vasc Biol. 1999 May;19(5):1284-90.

Group v secretory phospholipase A2 promotes atherosclerosis: evidence from genetically altered mice. Bostrom MA, Boyanovsky BB, Jordan CT, Wadsworth MP, Taatjes DJ, de Beer FC, Webb NR. Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):600-6. Epub 2007 Jan 4.

Analyses of group III secreted phospholipase A2 transgenic mice reveal potential participation of this enzyme in plasma lipoprotein modification, macrophage foam cell formation, and atherosclerosis. Sato H, Kato R, Isogai Y, Saka G, Ohtsuki M, Taketomi Y, Yamamoto K, Tsutsumi K, Yamada J, Masuda S, Ishikawa Y, Ishii T, Kobayashi T, Ikeda K, Taguchi R, Hatakeyama S, Hara S, Kudo I, Itabe H, Murakami M. J Biol Chem. 2008 Nov 28;283(48):33483-97. Epub 2008 Sep 18.

   sPLA2 used for risk stratification of patients with cardiovascular history

Circulating secretory phospholipase A2 activity predicts recurrent events in patients with severe acute coronary syndromes. Mallat Z, Steg PG, Benessiano J, Tanguy ML, Fox KA, Collet JP, Dabbous OH, Henry P, Carruthers KF, Dauphin A, Arguelles CS, Masliah J, Hugel B, Montalescot G, Freyssinet JM, Asselain B, Tedgui A. J Am Coll Cardiol. 2005 Oct 4;46(7):1249-57.

Impact of circulating secretory PhosphoLipase A2 (sPLA2) and Lipoprotein-associated phospholipase A2 (Lp-PLA2) activities on 6 months-survival, recurrent AMI and incident stroke in patients with AMI. Simon T, Benessiano J, et al. European Society of Cardiology Meeting, Munich, Germany, 2008, P1317

Association between type II secretory phospholipase A2 plasma concentrations and activity and cardiovascular events in patients with coronary heart disease. Koenig W, Vossen CY, Mallat Z, Brenner H, Benessiano J, Rothenbacher D. Eur Heart J. 2009 Nov;30(22):2742-8. Epub 2009 Aug 7

The Prognostic Utility of Secretory Phospholipase A2 in Patients With Stable Coronary Artery Disease. O'Donoghue ML; Mallat Z; Morrow DA; Benessiano J; Sloan S; Tedgui A; Sabatine MS Circulation. 2009;120:S452

Circulating secretory phospholipase A2 activity: an early prognostic marker in unselected patients presenting to the emergency department with suspected acute coronary syndrome. Benessiano J, Dehoux M, Bonnet P, Valentin E, Desplanques A and Steg PG. Presented at: XXèmes Journées Européennes de la Société Française de Cardiologie. Paris, France, 13-16 January 2010.

Serum Spla2 Activity, Spla2-IIa Mass and Oxldl Levels Are Related to the Significance of the Coronary Stenosis in Patients With Stable Coronary Artery Disease.Muller O, Ntalianis A, Delrue L, Mangiacapra F, Aaron P, Auer R, Hamilos M, Valentin E, Wijns W, De Bruyne B, Vanderheyden M, Barbato E, Bartunek JI. Circulation. 2010;122:A21315

The effect of high dose statin therapy on lipoprotein-associated and secretory phospholipase a2 mass and activity and ischemic events in patients with acute coronary syndromes. SUNG KEE RYU, Ziad Mallat, Gregory G. Schwartz, Joelle Benessiano, Alain Tedgui, Anders G. Olsson, Sotirios Tsimikas. J. Am. Coll. Cardiol. 2010;55;A165.E1546

Metabolic syndrome and carotid intima-media thickness in young adults: roles of apolipoprotein B, apolipoprotein A-I, C-reactive protein, and secretory phospholipase A2: the cardiovascular risk in young Finns study. Mattsson N, Magnussen CG, Rönnemaa T, Mallat Z, Benessiano J, Jula A, Taittonen L, Kähönen M, Juonala M, Viikari JS, Raitakari OT. Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1861-6. Epub 2010 Jun 10.

Comparison of the Effects of Combination Atorvastatin (40 mg) + Ezetimibe (10 mg) Versus Atorvastatin (40 mg) Alone on Secretory Phospholipase A2 Activity in Patients With Stable Coronary Artery Disease or Coronary Artery Disease Equivalent. Azar M, Valentin E, Badaoui G, Kassab R, Sarkis A, Azar RR. Am J Cardiol. 2011 Mar 23.

   sPLA2 used to screen healthy populations

Circulating secretory phospholipase A2 activity and risk of incident coronary events in healthy men and women: the EPIC-Norfolk study. Mallat Z, Benessiano J, Simon T, Ederhy S, et al. Arterioscler Thromb Vasc Biol. 2007 May;27(5):1177-83.

Oxidation-specific biomarkers, lipoprotein(a), and risk of fatal and nonfatal coronary events. Tsimikas S, Mallat Z, Talmud PJ, Kastelein JJ, Wareham NJ, Sandhu MS, Miller ER, Benessiano J, Tedgui A, Witztum JL, Khaw KT, Boekholdt SM. J Am Coll Cardiol. 2010 Sep 14;56(12):946-55.

   sPLA2 and Lp-PLA2 compared

Lipoprotein-associated and secreted phospholipases A2 in cardiovascular disease: roles as biological effectors and biomarkers. Mallat Z, Lambeau G, Tedgui A. Circulation. 2010 Nov 23;122(21):2183-200.