To hydrolyze or not to hydrolyze: the dilemma of platelet-activating factor acetylhydrolase

Marathe, Gopal K.; Pandit, Chaitanya; Lakshmikanth, Chikkamenahalli Lakshminarayana; Chaithra, Vyala Hanumanthareddy; Jacob, Shancy Petsel; D'Souza, Cletus Joseph Michael

doi:10.1194/jlr.r045492

Cited by 82 publications

(85 citation statements)

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“…These results suggested that PAF-AH may be a biomarker of vascular inflammation, rather than a causal pathway of CV diseases [23]. Therefore, high PAF-AH activity could reflect a response to pro-inflammatory stress characteristic both of atherosclerosis and APS [24]. …”

Section: Discussionmentioning

confidence: 99%

Exploring the plasmatic platelet-activating factor acetylhydrolase activity in patients with anti-phospholipid antibodies

Fabris

Cifù

Pistis

et al. 2017

Autoimmun Highlights

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PurposeTo explore the role of plasmatic platelet-activating factor acetylhydrolase (PAF-AH), a marker of cardiovascular risk, in patients with anti-phospholipid antibodies (aPL).MethodsPAF-AH activity was assessed in a series of 167 unselected patients screened for aPL in a context of thrombotic events, risk of thrombosis or obstetric complications and in 77 blood donors.Results116/167 patients showed positive results for at least one aPL among IgG/IgM anti-prothrombin/phosphatidylserine (aPS/PT), anti-cardiolipin (aCL), anti-beta2-glycoprotein I (aβ2GPI) or lupus anticoagulant (LAC), while 51/167 patients resulted aPL-negative. LAC+ patients disclosed higher PAF-AH than LAC-negative (22.1 ± 6.4 nmol/min/ml vs. 19.5 ± 4.1 nmol/min/ml; p = 0.0032), and aPL-negative patients (p = 0.03). Patients presenting positive IgG aβ2GPI disclosed higher PAF-AH than patients with only IgM aβ2GPI-positive antibodies (23.1 ± 7.2 nmol/min/ml vs. 20.1 ± 5.3 nmol/min/ml; p = 0.035), as well as than patients showing only isolated LAC, aCL or aPS/PT (16.9 ± 3.8 nmol/min/ml; p = 0.003).ConclusionsPAF-AH plasmatic activity is particularly up-regulated in LAC+ and in aβ2GPI IgG+ patients, possibly representing an alternative prognostic biomarker for the therapeutic management of APS patients.

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Section: Discussionmentioning

confidence: 99%

Exploring the plasmatic platelet-activating factor acetylhydrolase activity in patients with anti-phospholipid antibodies

Fabris

Cifù

Pistis

et al. 2017

Autoimmun Highlights

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“…In this issue of the Journal of Lipid Research , Marathe et al ( 1 ) provide their views on the role of PAF-AH in infl ammatory responses, with a focus on CVD. The authors make several key points and offer a seldom encountered perspective that takes into consideration the origin and wide range of substrates hydrolyzed by PAF-AH, the physiological meaning of studies involving one of the products of the reaction (lysoPAF/lysoPC), and the impact of receptors that recognize substrates and products on downstream signaling events.…”

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confidence: 99%

“…In addition, the relationship between circulating and tissue PAF-AH and OxPLs has not been critically evaluated, and this issue raises important questions regarding by guest, on April 29, 2019 www.jlr.org Downloaded from Commentary the impact of enzyme, substrate, and products in different biologic compartments. The article by Marathe et al ( 1 ) discusses some of these variables in the intricate biochemistry and biology of PAF-AH, PAF, and related lipids.…”

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confidence: 99%

Unraveling the PAF-AH/Lp-PLA2 controversy

Stafforini

Zimmerman

2014

Journal of Lipid Research

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“…In addition, Lp‐PLA2 could efficiently hydrolyze short‐chain diacylglycerols, triacylglycerols, and acetylated alkanols, signifying that a polar headgroup might not be required for Lp‐PLA2 substrates. Furthermore, the enzyme shows a weak specificity at the sn ‐1 position, as it could not distinguish ester from ether at the sn ‐1 position of PAF or PAF analogs . Apparently, glycerides with a sn ‐2 ester and a reasonably hydrophobic sn ‐1 residue would be efficient substrates of Lp‐PLA2.…”

Section: Biochemical Properties and Structural Characteristicsmentioning

confidence: 99%

Lipoprotein‐associated phospholipase A2: The story continues

Huang

Wang

Shen

2019

Medicinal Research Reviews

125

140

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Inflammation is thought to play an important role in the pathogenesis of vascular diseases. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation‐related diseases, mainly atherosclerosis. Although darapladib, the most advanced Lp‐PLA2 inhibitor, failed to meet the primary endpoints of two large phase III trials in atherosclerosis patients cotreated with standard medical care, the research on Lp‐PLA2 has not been terminated. Novel pathogenic, epidemiologic, genetic, and crystallographic studies regarding Lp‐PLA2 have been reported recently, while novel inhibitors were identified through a fragment‐based lead discovery strategy. More strikingly, recent clinical and preclinical studies revealed that Lp‐PLA2 inhibition showed promising therapeutic effects in diabetic macular edema and Alzheimer's disease. In this review, we not only summarized the knowledge of Lp‐PLA2 established in the past decades but also emphasized new findings in recent years. We hope this review could be valuable for helping researchers acquire a much deeper insight into the nature of Lp‐PLA2, identify more potent and selective Lp‐PLA2 inhibitors, and discover the potential indications of Lp‐PLA2 inhibitors.

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To hydrolyze or not to hydrolyze: the dilemma of platelet-activating factor acetylhydrolase

Cited by 82 publications

References 84 publications

Exploring the plasmatic platelet-activating factor acetylhydrolase activity in patients with anti-phospholipid antibodies

Exploring the plasmatic platelet-activating factor acetylhydrolase activity in patients with anti-phospholipid antibodies

Unraveling the PAF-AH/Lp-PLA2 controversy

Lipoprotein‐associated phospholipase A2: The story continues

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