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Migraine in Patients Undergoing PFO Closure : Characterization of a Platelet-Associated Pathophysiological Mechanism: The LEARNER Study

ABSTRACT: Visual Abstract Highlights • Patients experiencing MHA-PFO on aspirin are characterized by a marked thrombin generation capacity sustained by an elevated number of platelets and MVs expressing a functionally active tissue factor.• MHA-PFO patients are also characterized by an altered oxidative stress status, ie, increased platelet ROS production and blood GSSG/GSH ratio.• This prothrombotic condition fully reverts upon PFO closure and is associated with 100% migraine remission.• MHA-PFO plasma and GSSG, added to blood of healthy subjects, mirrored the in vivo platelet activation and this effect is blunted by N-acetylcysteine, thus supporting the etiopathogenetic role of oxidative stress in this clinical setting.• Aspirin had little effect on the platelet prothrombotic phenotype that was better controlled by P2Y12 antagonist. Summary The association between migraine and patent foramen ovale (PFO) has been documented. We aimed to investigate platelet activation, prothrombotic phenotype, and oxidative stress status of migraineurs with PFO on 100 mg/day aspirin, before and 6 months after PFO closure. Data show that, before PFO closure, expression of the classical platelet activation markers is comparable in patients and aspirin-treated healthy subjects. Conversely, MHA-PFO patients display an increased prothrombotic phenotype (higher tissue factorpos platelets and microvesicles and thrombin-generation potential), sustained by an altered oxidative stress status. This phenotype, which is more controlled by P2Y12-blockade than by aspirin, reverted after PFO closure together with a complete migraine remission. (pLatelEts And MigRaine iN patEnt foRamen Ovale [LEARNER]; NCT03521193)

SUBMITTER: Trabattoni D

PROVIDER: S-EPMC9270571 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe anatomy of PFO suggests that it can allow thrombi and potentially harmful circulatory factors to travel directly from the venous to the arterial circulation - altering circulatory phenotype. Our previous publication using high-resolution LC-MS/MS to profile protein and peptide expression patterns in plasma showed that albumin was relatively increased in donor samples from PFO-related than other types of ischemic strokes. Since albumin binds a host of molecules and acts as a carrier for lipoproteins, small molecules and drugs, we decided to investigate the albumin-bound proteins (in a similar sample cohort) in an effort to unravel biological changes and potentially discover biomarkers related to PFO-related stroke and PFO endovascular closure.MethodsThe method used in this study combined albumin immuno-enrichment with high resolution LC-MS in order to specifically capture and quantify the albumin-bound proteins. Subsequently, we measured cholesterol and HDL in a larger, separate cohort of PFO stroke patients, pre and post closure.ResultsThe results demonstrated that a number of proteins were specifically associated with albumin in samples with and without endovascular closure of the PFO, and that the protein profiles were very different. Eight proteins, typically associated with HDL were common to both sample sets and quantitatively differently abundant. Pathway analysis of the MS results suggested that enhanced cholesterol efflux and reduced lipid oxidation were associated with PFO closure. Measurement of total cholesterol and HDL in a larger cohort of PFO closure samples using a colorimetric assay was consistent with the proteomic predictions.ConclusionsThe collective data presented in this study demonstrate that analysis of albumin-bound proteins could provide a valuable tool for biomarker discovery on the effects of PFO endovascular closure. In addition, the results suggest that PFO endovascular closure can potentially have effects on HDL, cholesterol and albumin-bound ApoA-I abundance, therefore possibly providing benefits in cardioprotective functions.

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Migraine in Patients Undergoing PFO Closure : Characterization of a Platelet-Associated Pathophysiological Mechanism: The LEARNER Study

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