Lipoprotein-Associated and Secreted Phospholipases A
            <sub>2</sub>
            in Cardiovascular Disease

Mallat, Ziad; Lambeau, Gérard; Tedgui, Alain

doi:10.1161/circulationaha.110.936393

Cited by 162 publications

(118 citation statements)

References 167 publications

(169 reference statements)

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“…Beside the above, our results show that the activity of sPLA 2 is correlated with plasmalogens and malondialdehyde in LDL, suggesting that this enzyme catalyses the hydrolysis of oxidised phospholipids in LDL [40]. The correlation between the activity of sPLA 2 and waist circumference is in line with the association of sPLA 2 with the metabolic syndrome [41].…”

Section: Discussionsupporting

confidence: 81%

LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets

et al. 2011

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Aims/hypothesis This study assessed oxidative stress in LDL from obese patients with the metabolic syndrome and compared it with that in LDL from type 2 diabetic patients or control volunteers. It also determined the effect on platelets of LDL from the three groups. Methods The profiles of lipids, fatty acids and fatty acid oxidation products were determined in LDL isolated from plasma of patients with the metabolic syndrome, patients with type 2 diabetes and volunteers (n=10 per group). The effects of LDL from the participant groups on the platelet arachidonic acid signalling cascade and aggregation were investigated. Results Compared with LDL from control volunteers, LDL from obese metabolic syndrome and type 2 diabetic patients had lower cholesteryl ester, higher triacylglycerol and lower ethanolamine plasmalogen levels. Proportions of linoleic acid were decreased in phosphatidylcholine and cholesteryl esters in LDL from both patient groups. Among the markers of lipid peroxidation, oxidation products of linoleic acid (hydroxy-octadecadienoic acids) and malondialdehyde were increased by 59% and twofold, respectively in LDL from metabolic syndrome and type 2 diabetic patients. LDL from metabolic syndrome and type 2 diabetic patients were equally potent in activating the platelet arachidonic acid signalling cascade through increased phosphorylation of p38 mitogen-activated protein kinase and cytosolic phospholipase A 2 , and through increased thromboxane B 2 formation. LDL from patients with the metabolic syndrome and type 2 diabetes potentiated platelet aggregation by threefold and 3.5-fold respectively, whereas control LDL had no activating effects on platelets. Conclusions/interpretation The metabolic syndrome in obese patients, without or with diabetes, is associated with increased oxidative stress in LDL, which triggers platelet activation.

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Section: Discussionsupporting

confidence: 81%

LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets

et al. 2011

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“…Platelet-activating factor acetyl hydrolase (PAF-AH) equally termed lipoprotein-associated phospholipase A 2 (LpPLA 2 ) is a calcium-independent, N-glycosylated enzyme, which degrades PAF by hydrolysing the sn-2 ester bond to yield biologically inactive lyso-PAF (Mallat et al 2010). The enzyme cleaves phospholipid substrates with a short residue at the sn-2 position and can therefore hydrolyse proinflammatory oxidised short-chain phospholipids; however, it is inactive against long-chain non-oxidised phospholipids.…”

Section: Enzymesmentioning

confidence: 99%

Structure of HDL: Particle Subclasses and Molecular Components

Kontush

Lindahl

Lhomme

et al. 2014

Handbook of Experimental Pharmacology

228

226

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“…Higher levels of lipoprotein‐associated phospholipase A 2 (Lp‐PLA 2 ) activity have also been associated with an increased risk of coronary events in healthy elderly persons and in patients with stable CHD 6, 7, 8, 9. There is some evidence that Lp‐PLA 2 might be part of the atherosclerotic process and may contribute to plaque destabilization through inflammatory activity in the atherosclerotic lesions 10, 11, 12. Consequently, it is important to further evaluate the independent prognostic value of Lp‐PLA 2 activity as a risk marker for individual nonfatal and fatal cardiovascular events in large long‐term prospective studies of patients with CHD in addition to considering information provided by other prognostic biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Lipoprotein‐Associated Phospholipase A ₂ Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

Wallentin

Held

Armstrong

et al. 2016

JAHA

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BackgroundWe evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA 2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA 2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial.Methods and ResultsPlasma Lp‐PLA 2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA 2 activity levels and outcomes. At baseline, the median Lp‐PLA 2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA 2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA 2 activity. There were no associations between on‐treatment Lp‐PLA 2 activity or changes of Lp‐PLA 2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA 2 activity or changes in Lp‐PLA 2 activity levels and the effects of darapladib on outcomes.ConclusionsAlthough high Lp‐PLA 2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA 2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA 2 activity.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903.

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Lipoprotein-Associated and Secreted Phospholipases A ₂ in Cardiovascular Disease

Cited by 162 publications

References 167 publications

LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets

LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets

Structure of HDL: Particle Subclasses and Molecular Components

Lipoprotein‐Associated Phospholipase A ₂ Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

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Lipoprotein-Associated and Secreted Phospholipases A 2 in Cardiovascular Disease

Cited by 162 publications

References 167 publications

LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets

LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets

Structure of HDL: Particle Subclasses and Molecular Components

Lipoprotein‐Associated Phospholipase A 2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

Contact Info

Product

Resources

About

Lipoprotein-Associated and Secreted Phospholipases A ₂ in Cardiovascular Disease

Lipoprotein‐Associated Phospholipase A ₂ Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease