Lipoprotein-associated phospholipase A2

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.

PLA2G7
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3D59, 3D5E, 3F96, 3F97, 3F98, 3F9C, 5JAU, 5JAR, 5I9I, 5JAD, 5JAO, 5I8P, 5JAS, 5JAN, 5JAL, 5JAH, 5JAP, 5JAT
Identifiers
Aliases	PLA2G7, LDL-PLA2, LP-PLA2, PAFAD, PAFAH, Lipoprotein-associated phospholipase A2, phospholipase A2 group VII
External IDs	OMIM: 601690; MGI: 1351327; HomoloGene: 3725; GeneCards: PLA2G7; OMA:PLA2G7 - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p12.3 Start 46,704,201 bp[1] End 46,735,693 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 B3 Start 43,878,989 bp[2] End 43,923,092 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in amniotic fluid decidua appendix monocyte lymph node spleen mucosa of sigmoid colon rectum endometrium palpebral conjunctiva Top expressed in stroma of bone marrow deep cerebellar nuclei medial vestibular nucleus lobe of cerebellum cerebellar vermis dorsal tegmental nucleus stria vascularis pontine nuclei vestibular sensory epithelium globus pallidus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium-independent phospholipase A2 activity hydrolase activity phospholipid binding hydrolase activity, acting on ester bonds 1-alkyl-2-acetylglycerophosphocholine esterase activity Cellular component cytoplasm extracellular region low-density lipoprotein particle extracellular space Biological process lipid catabolic process lipid oxidation plasma lipoprotein particle oxidation positive regulation of monocyte chemotaxis positive regulation of inflammatory response low-density lipoprotein particle remodeling lipid metabolism platelet activating factor metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7941 27226 Ensembl ENSG00000146070 ENSMUSG00000023913 UniProt Q13093 Q60963 RefSeq (mRNA) NM_001168357 NM_005084 NM_013737 RefSeq (protein) NP_001161829 NP_005075 NP_038765 Location (UCSC) Chr 6: 46.7 – 46.74 Mb Chr 17: 43.88 – 43.92 Mb PubMed search [3] [4]
Wikidata
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Function

In the blood, Lp-PLA₂ 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

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, two 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

• Darapladib