Lipoprotein-associated phospholipase A2

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Phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma)
Protein PLA2G7 PDB 3D59.png
Rendering based on PDB 3D59.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PLA2G7 ; LDL-PLA2; LP-PLA2; PAFAD; PAFAH
External IDs OMIM601690 MGI1351327 HomoloGene3725 ChEMBL: 3514 GeneCards: PLA2G7 Gene
EC number 3.1.1.47
RNA expression pattern
PBB GE PLA2G7 206214 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7941 27226
Ensembl ENSG00000146070 ENSMUSG00000023913
UniProt Q13093 Q60963
RefSeq (mRNA) NM_001168357 NM_013737
RefSeq (protein) NP_001161829 NP_038765
Location (UCSC) Chr 6:
46.67 – 46.7 Mb
Chr 17:
43.57 – 43.61 Mb
PubMed search [1] [2]

Lipoprotein-associated phospholipase A2 (Lp-PLA2) also known as platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 enzyme that in humans is encoded by the PLA2G7 gene.[1][2] Lp-PLA2 is a 45-kDa protein of 441 amino acids.[3] It is one of several PAF acetylhydrolases.

Function[edit]

In the blood it travels mainly with low-density lipoprotein (LDL). Less than 20% is associated with high-density lipoprotein HDL. It is an enzyme produced by inflammatory cells and hydrolyzes oxidized phospholipids in LDL.

Lp-PLA2 is platelet-activating factor (PAF) acetylhydrolase (EC 3.1.1.47), a secreted enzyme that catalyzes the degradation of PAF to inactive products by hydrolysis of the acetyl group at the sn-2 position, producing the biologically inactive products LYSO-PAF and acetate.[4]

Clinical significance[edit]

Lp-PLA2 is involved in the development of atherosclerosis,[3] an observation that has prompted interest as a possible therapeutic target (see, e.g. the investigational drug Darapladib). In human atherosclerotic lesions, 2 main sources of Lp-PLA2 can be identified, including that which is brought into the intima bound to LDL (from the circulation), and that which is synthesized de novo by plaque inflammatory cells (macrophages, T cells, mast cells)."

It is used as a marker for cardiac disease.[5]

A meta-analysis involving a total of 79,036 participants in 32 prospective studies found that Lp-PLA2 levels are positively correlated with increased risk of developing coronary heart disease and stroke.[6]

See also[edit]

References[edit]

  1. ^ Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens LS, Zimmerman GA (April 1995). "Anti-inflammatory properties of a platelet-activating factor acetylhydrolase". Nature 374 (6522): 549–53. doi:10.1038/374549a0. PMID 7700381. 
  2. ^ Tew DG, Southan C, Rice SQ, Lawrence MP, Li H, Boyd HF, Moores K, Gloger IS, Macphee CH (April 1996). "Purification, properties, sequencing, and cloning of a lipoprotein-associated, serine-dependent phospholipase involved in the oxidative modification of low-density lipoproteins". Arterioscler. Thromb. Vasc. Biol. 16 (4): 591–9. doi:10.1161/01.ATV.16.4.591. PMID 8624782. 
  3. ^ a b Zalewski A, Macphee C (May 2005). "Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target". Arterioscler. Thromb. Vasc. Biol. 25 (5): 923–31. doi:10.1161/01.ATV.0000160551.21962.a7. PMID 15731492. 
  4. ^ "Entrez Gene: PLA2G7 phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma)". 
  5. ^ Mohler ER, Ballantyne CM, Davidson MH, Hanefeld M, Ruilope LM, Johnson JL, Zalewski A (April 2008). "The effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study". J. Am. Coll. Cardiol. 51 (17): 1632–41. doi:10.1016/j.jacc.2007.11.079. PMID 18436114. 
  6. ^ The Lp-PLA2 Studies Collaboration (2010). "Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies". The Lancet 375 (9725): 1536–1544. doi:10.1016/S0140-6736(10)60319-4. Lay summaryBBC News. 

Further reading[edit]