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Literature summary for 3.1.1.4 extracted from
- Phospholipase A2 inhibitors (2009), Curr. Opin. Lipidol., 20, 327-332.
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | sPLA2s and Lp-PLA2 inhibitors darapladib and varespladib emerge as promising therapeutical options for treating patients with coronary artery disease. Lp-PLA2 inhibition may favorably affect rupture-prone lesions | Homo sapiens |
| medicine | combination of sPLA2 activity and cardiovascular reactive protein values is more useful to detect incident risk of coronary artery disease than either biomarker alone. Prognostic value of plasma concentrations and activity of Lp-PLA2 in patients with coronary heart disease | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| (3-aminooxalyl-1-benzyl-2-ethyl-6-methyl-1H-indol-4-yl)oxyacetic acid methyl ester | LY374388, potent sPLA2 inhibitor | Homo sapiens |  |
| 1-H-indole-3-glyoxamide | varespladib methyl, potent sPLA2 inhibitor | Homo sapiens | |
| 3-[1-benzyl-3-(carbamoylmethyl)-2-ethylindol-5-yl]oxypropylphosphonic acid | LY311727, potent sPLA2 inhibitor | Homo sapiens | |
| darapladib | inhibits Lp-PLA2 activity by 59% | Homo sapiens | |
| darapladib | reduces development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic swine, specifically reduces plaque area and necrotic core area and medial destruction, resulting in fewer lesions with an unstable phenotype | Sus scrofa | |
| indoxam | most potent sPLA2 inhibitor | Homo sapiens | |
| Me-Indoxam | most potent sPLA2 inhibitor | Homo sapiens | |
| additional information | substituted indoles and indolizines are the most potent sPLA2 inhibitors | Homo sapiens | |
| rilapladib | - |
Sus scrofa | |
| sodium 2-(1-benzyl-2-ethyl)-3-oxamoylindol-4-yl oxyacetate | varespladib sodium or LY315920, most potent sPLA2 inhibitor | Homo sapiens | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Sus scrofa | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| inflammatory cell | Lp-PLA2, cells involved in atherogenesis | Homo sapiens | - |
| additional information | Lp-PLA2 in pathologic intimal thickening plaques is nearly absent | Homo sapiens | - |
| myocardium | sPLA2 present in the limits of the infarcted myocardium | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| phospholipids + H2O | Lp-PLA2 rapidly degrades oxidatively modified phospholipids in modified low density lipoprotein leading to formation of proinflammatory and cytotoxic products (i.e. lysophosphatidylcholine) and oxidized nonesterified fatty acids | Homo sapiens | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| lipoprotein-associated phospholipase A2 | - |
Sus scrofa |
| lipoprotein-associated phospholipase A2 | Lp-PLA2 | Homo sapiens |
| Lp-PLA2 | - |
Homo sapiens |
| Lp-PLA2 | - |
Sus scrofa |
| PAF-AH | - |
Sus scrofa |
| PAF-AH | Lp-PLA2 | Homo sapiens |
| phospholipase A2 | - |
Homo sapiens |
| phospholipase A2 | - |
Sus scrofa |
| platelet-activating factor acetylhydrolase | - |
Sus scrofa |
| platlet-activating factor acetylhydrolase | Lp-PLA2 | Homo sapiens |
| secreted PLA2 | sPLA2 | Homo sapiens |
| sPLA2 | - |
Homo sapiens |
| sPLA2-IIA | sPLA2 | Homo sapiens |
| type VIIA PLA2 | - |
Sus scrofa |
| type VIIA PLA2 | Lp-PLA2 | Homo sapiens |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | Lp-PLA2 is highly expressed in the necrotic core of atherosclerotic lesions | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| metabolism | sPLA2s and Lp-PLA2 produce biologically active metabolites that are involved in several phases of the atherosclerosis process | Homo sapiens |
| physiological function | sPLA2s (sPLA2-IIA) and Lp-PLA2 are associated with atherogenesis and its complications. Increased levels of these two phospholipases are related with an increase in complex coronary lesions and increase in major cardiovascular clinical events, respectively. sPLA2 may play an important role in atherogenesis by modifying low density lipoprotein particles in the arterial wall, thereby enhancing their aggregation, retention, and macrophage uptake. Cytotoxic compounds from Lp-PLA2 play an important in plaque vulnerability, Lp-PLA2 has a predominantly proinflammatory role in atherogenesis | Homo sapiens |
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