Lipoprotein-associated phospholipase A2: Difference between revisions

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== Function ==
== Function ==


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 cell]]s and hydrolyzes oxidized [[phospholipid]]s in LDL.
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.<ref>The role of lipoprotein-associated phospholipase A2 in atherosclerosis may depend on its lipoprotein carrier in plasma. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Volume 1791, Issue 5, May 2009, Pages 327-338 {{PMID|19272461}} DOI: 10.1016/j.bbalip.2009.02.015</ref> It is an enzyme produced by [[inflammatory cell]]s and hydrolyzes oxidized [[phospholipid]]s in LDL.


Lp-PLA<sub>2</sub> is platelet-activating factor ([[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.<ref name="entrez">{{cite web | title = Entrez Gene: PLA2G7 phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7941| accessdate = }}</ref>
Lp-PLA<sub>2</sub> is platelet-activating factor ([[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.<ref name="entrez">{{cite web | title = Entrez Gene: PLA2G7 phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7941| accessdate = }}</ref>
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== See also ==
== See also ==
*[[darapladib]]
*[[Darapladib]]


== References ==
== References ==

Latest revision as of 06:04, 4 August 2018

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SpeciesHumanMouse
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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

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.[4] 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.[5]

Clinical significance

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.[6]

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.[7]

See also

References

  1. Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens LS, Zimmerman GA, Yamada Y, McIntyre TM, Prescott SM, Gray PW (Apr 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 (Apr 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.
  3. 3.0 3.1 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.
  4. The role of lipoprotein-associated phospholipase A2 in atherosclerosis may depend on its lipoprotein carrier in plasma. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids Volume 1791, Issue 5, May 2009, Pages 327-338 PMID 19272461 DOI: 10.1016/j.bbalip.2009.02.015
  5. "Entrez Gene: PLA2G7 phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma)".
  6. Mohler ER, Ballantyne CM, Davidson MH, Hanefeld M, Ruilope LM, Johnson JL, Zalewski A (Apr 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.
  7. 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. PMC 2864403. PMID 20435228. Lay summaryBBC News.

Further reading