Lipoprotein-associated phospholipase A2

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PLA2G7
Protein PLA2G7 PDB 3D59.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPLA2G7, LDL-PLA2, LP-PLA2, PAFAD, PAFAH, Lipoprotein-associated phospholipase A2, phospholipase A2 group VII
External IDsOMIM: 601690 MGI: 1351327 HomoloGene: 3725 GeneCards: PLA2G7
Gene location (Human)
Chromosome 6 (human)
Chr.Chromosome 6 (human)[1]
Chromosome 6 (human)
Genomic location for PLA2G7
Genomic location for PLA2G7
Band6p12.3Start46,704,201 bp[1]
End46,735,693 bp[1]
RNA expression pattern
PBB GE PLA2G7 206214 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001168357
NM_005084

NM_013737

RefSeq (protein)

NP_001161829
NP_005075

NP_038765

Location (UCSC)Chr 6: 46.7 – 46.74 MbChr 17: 43.57 – 43.61 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6] Lp-PLA2 is a 45-kDa protein of 441 amino acids.[7] 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. Several lines of evidence suggest that HDL-associated Lp-PLA2 may substantially contribute to the HDL antiatherogenic activities.[8] 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.[9]

Clinical significance[edit]

Lp-PLA2 is involved in the development of atherosclerosis,[7] 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.[10]

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.[11]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000146070 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023913 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, et al. (April 1995). "Anti-inflammatory properties of a platelet-activating factor acetylhydrolase". Nature. 374 (6522): 549–53. doi:10.1038/374549a0. PMID 7700381.
  6. ^ Tew DG, Southan C, Rice SQ, Lawrence MP, Li H, Boyd HF, et al. (April 1996). "Purification, properties, sequencing, and cloning of a lipoprotein-associated, serine-dependent phospholipase involved in the oxidative modification of low-density lipoproteins". Arteriosclerosis, Thrombosis, and Vascular Biology. 16 (4): 591–9. doi:10.1161/01.ATV.16.4.591. PMID 8624782.
  7. ^ a b Zalewski A, Macphee C (May 2005). "Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target". Arteriosclerosis, Thrombosis, and Vascular Biology. 25 (5): 923–31. doi:10.1161/01.ATV.0000160551.21962.a7. PMID 15731492.
  8. ^ Tellis CC, Tselepis AD (May 2009). "The role of lipoprotein-associated phospholipase A2 in atherosclerosis may depend on its lipoprotein carrier in plasma". Biochimica et Biophysica Acta. 1791 (5): 327–38. doi:10.1016/j.bbalip.2009.02.015. PMID 19272461.
  9. ^ "Entrez Gene: PLA2G7 phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma)".
  10. ^ 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". Journal of the American College of Cardiology. 51 (17): 1632–41. doi:10.1016/j.jacc.2007.11.079. PMID 18436114.
  11. ^ Thompson A, Gao P, Orfei L, Watson S, Di Angelantonio E, Kaptoge S, et al. (May 2010). "Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies". Lancet. 375 (9725): 1536–44. doi:10.1016/S0140-6736(10)60319-4. PMC 2864403. PMID 20435228. Lay summaryBBC News.

Further reading[edit]