Lipoprotein-associated phospholipase A2 (Lp-PLA2): a review of its role and significance as a cardiovascular biomarker

Vittos, Oana; Toana, B; Vittos, Alexandros; Moldoveanu, E

doi:10.3109/1354750x.2012.664170

Cited by 50 publications

(47 citation statements)

References 86 publications

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“…Indeed the biological role of Lp-PLA 2 is controversial since the anti-or proatherogenic functions of this enzyme have been proposed. Lp-PLA 2 might be antiatherogenic if it hydrolyzes PAF, a well-known proinfammatory factor that contributes to in ammation and atherosclerosis [22,26]. Despite this, individuals with reduced levels of Lp-PLA 2 activity do not display the rampant in ammatory responses anticipated from uncontrolled PAF accumulation [12], and the acute bronchoconstrictive response to inhaled PAF does not vary in these individuals [12,27,28].…”

Section: Discussionmentioning

confidence: 99%

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Zhang

Zhang²,

Sun³

et al. 2013

CIM

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Purpose: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the pathogenesis of atherosclerosis, especially in advanced plaques. In the present study, the abilities of darapladib, a selective Lp-PLA2 inhibitor, and lentivirus-mediated Lp-PLA2 silencing on in ammation and atherosclerosis in apolipoprotein E-de cient mice were compared.Methods: Apolipoprotein E-de cient mice were fed on a high-fat diet and a constrictive collar was placed around the le carotid artery to induce plaque formation. e mice were randomly divided into control, negative control (NC), darapladib and RNA interference (RNAi) groups. Eight weeks a er surgery, lentivirus-mediated RNAi construct or darapladib were used to decrease the expression of Lp-PLA2. Plaques were collected ve weeks later for histological analysis. In ammatory gene expression in the atherosclerotic lesions were then determined at the mRNA and protein level.Results: e expression of pro-in ammatory cytokines was signi cantly reduced in the treatment group, compared to nontreatment group, whereas the plasma concentration of anti-in ammatory cytokines increased markedly. Moreover, our results demonstrated a signi cant reduction in plaque lipid content, as well as a rise in collagen content following Lp-PLA2 inhibition. Interestingly, when comparing the two methods of Lp-PLA2 inhibition, animals treated with Lp-PLA2 RNAi were found to exhibit lower plaque areas and enhanced improvement of plaque stability as compared with animals treated with darapladib. Darapladib had no attenuating e ect on atherosclerotic plaque area. ese therapeutic e ects were independent of plasma lipoprotein levels.Conclusions: Lp-PLA2 inhibition by darapladib or lentivirus-mediated RNAi ameliorated in ammation and atherosclerosis in apolipoprotein E-de cient mice. e e ect was more prominent in the RNAi group.

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Section: Discussionmentioning

confidence: 99%

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Zhang

Zhang²,

Sun³

et al. 2013

CIM

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“…Additionally, Lyso-PC can upregulate PAF-AH activity, resulting in a vicious cycle in which pro-inflammatory mediators are upregulated, contributing to plaque progression and destabilization (19). In addition, oxNEFAs, another detrimental substrate of PAF-AH, can promote atherosclerosis by increasing oxidative stress and the presence of oxidized LDL and other lipoproteins in the plasma and arterial walls, thereby initiating fatty streak formation (20).…”

Section: Discussionmentioning

confidence: 99%

Associations of platelet-activating factor acetylhydrolase gene polymorphisms with risk of ischemic stroke

2015

Biomedical Reports

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Abstract. Platelet-activating factor acetylhydrolase (PAF-AH) has an important function in the pathogenesis of ischemic stroke. The aim of the present study was to investigate the correlation between the variation of polymorphisms (R92H and V279F) in PAF-AH and ischemic stroke. A total of 375 patients with ischemic stroke and 370 healthy controls were recruited into the study. Polymorphisms of V279F and R92H in PAF-AH were detected by polymerase chain reaction and DNA direct sequencing method. No significant association was observed between V279F and ischemic stroke. However, the RH+HH genotype, RH genotype and H allele of R92H were significantly associated with an increased risk of ischemic stroke (P=0.02, P=0.03 and P=0.02, respectively), In addition, these correlations remained following adjustment for confounding risk factors of stroke. Furthermore, subgroup analysis showed that a significant association with R92H was identified in the large-artery atherosclerotic stroke subgroup. These findings indicated that variation of R92H in the PAF-AH gene may contribute to ischemic stroke susceptibility in the population studied.

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“…4,5 It is generally known to catalyze the hydrolysis of oxidized low density lipoproteins (LDLs) and it is the reason why Lp-PLA 2 is considered as a marker for cardiovascular diseases. 2,6 After LDL oxidation, Lp-PLA 2 generates two fatty acid related products; oxidized nonesterified fatty acids and lysophosphatidylcholine. 7,8 Both of them have proapoptotic and proinflammatory activities and recruit macrophages for the development of atherosclerotic plaques.…”

Section: Introductionmentioning

confidence: 99%

“…Among the families, the two families of PLA 2 , secretory PLA 2 (sPLA 2 ) and lipoprotein-associated PLA 2 (Lp-PLA 2 ), have been evaluated and regarded as biomarkers of cardiovascular related diseases. [1][2][3] Lp-PLA 2 is also known as platelet-activating factor acetylhydrolase (PAF-AH) which is a crucial enzyme in atherosclerosis. 4,5 It is generally known to catalyze the hydrolysis of oxidized low density lipoproteins (LDLs) and it is the reason why Lp-PLA 2 is considered as a marker for cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] The five main families of phospholipases have been defined of their physiological roles. Among the families, the two families of PLA 2 , secretory PLA 2 (sPLA 2 ) and lipoprotein-associated PLA 2 (Lp-PLA 2 ), have been evaluated and regarded as biomarkers of cardiovascular related diseases. [1][2][3] Lp-PLA 2 is also known as platelet-activating factor acetylhydrolase (PAF-AH) which is a crucial enzyme in atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

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Darapladib Binds to Lipoprotein-Associated Phospholipase A2 with Meaningful Interactions

Rok¹,

Kim

Chang

et al. 2014

Bulletin of the Korean Chemical Society

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Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) is a crucial enzyme in atherosclerosis as a potential drug target. The most remarkable Lp-PLA 2 inhibitory drug is Darapladib. We determined the binding pose of Darapladib to Lp-PLA 2 through docking study. Darapladib formed two hydrogen bonding interactions with the side chain of Tyr160 and Gln352 and several pi-pi interactions with aromatic and aliphatic hydrophobic residues of Lp-PLA 2 . It is known that the dietylpropan-amine moiety of Darapladib has influence on the improvement of its oral bioavailability and we supposed this in our docking results.

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Lipoprotein-associated phospholipase A2 (Lp-PLA2): a review of its role and significance as a cardiovascular biomarker

Abstract: The role of Lp-PLA2 as a significant biomarker of vascular inflammation was confirmed, and Lp-PLA2 seems to be closely correlated to cardiovascular events. It may be an important therapeutic target and may have an important role in prevention, risk stratification and personalised medicine.

Cited by 50 publications

References 86 publications

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Amelioration of atherosclerosis in apolipoprotein E-deficient mice by inhibition of lipoprotein-associated phospholipase A2

Associations of platelet-activating factor acetylhydrolase gene polymorphisms with risk of ischemic stroke

Darapladib Binds to Lipoprotein-Associated Phospholipase A2 with Meaningful Interactions

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