Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) also known as platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A₂

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that in humans is encoded by the ''PLA2G7''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. Lp-PLA₂ is a 45-kDa

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

of 441

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s. It is one of several

PAF acetylhydrolase The enzyme 1-alkyl-2-acetylglycerophosphocholine esterase (EC 3.1.1.47) catalyzes the reaction :1-alkyl-2-acetyl-''sn''-glycero-3-phosphocholine + H2O \rightleftharpoons 1-alkyl-''sn''-glycero-3-phosphocholine + acetate The former is also know ...

Function

In the blood Lp-PLA₂ travels mainly with

low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

(LDL). Less than 20% is associated with

high-density lipoprotein High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are ty ...

HDL. Several lines of evidence suggest that HDL-associated Lp-PLA2 may substantially contribute to the HDL antiatherogenic activities. It is an enzyme produced by

inflammatory cell White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

s and hydrolyzes oxidized

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

s 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.

Clinical significance

Lp-PLA₂ is involved in the development of

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...

, an observation that has prompted interest as a possible therapeutic target (see, e.g. the investigational drug

Darapladib Darapladib is an inhibitor lipoprotein-associated phospholipase A2 (Lp-PLA2) that is in development as a drug for treatment of atherosclerosis. It was discovered by Human Genome Sciences in collaboration with GlaxoSmithKline (GSK). In November ...

). In human atherosclerotic lesions, 2 main sources of Lp-PLA₂ can be identified, including that which is brought into the

intima The tunica intima (New Latin "inner coat"), or intima for short, is the innermost tunica (layer) of an artery or vein. It is made up of one layer of endothelial cells and is supported by an internal elastic lamina. The endothelial cells are in ...

bound to LDL (from the circulation), and that which is synthesized de novo by plaque inflammatory cells (

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s, T cells, mast cells)." It is used as a marker for cardiac disease. A

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

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 Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...

and

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

. *

Function

Clinical significance

See also

References

Further reading