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Protease-activated receptor-2: Role in asthma pathogenesis and utility as a biomarker of disease severity.

ABSTRACT: PAR₂, a receptor activated by serine proteases, has primarily pro-inflammatory roles in the airways and may play a role in asthma pathogenesis. PAR₂ exerts its effects in the lungs through activation of a variety of airway cells, but also activation of circulating immune cells. There is evidence that PAR₂ expression increases in asthma and other inflammatory diseases, although the regulation of PAR₂ expression is not fully understood. Here we review the available literature on the potential role of PAR₂ in asthma pathogenesis and propose a model of PAR₂-mediated development of allergic sensitization. We also propose, based on our previous work, that PAR₂ expression on peripheral blood monocyte subsets has the potential to serve as a biomarker of asthma severity and/or control.

SUBMITTER: Gandhi VD

PROVIDER: S-EPMC9372307 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Protease-activated receptor-2: Role in asthma pathogenesis and utility as a biomarker of disease severity.

Gandhi Vivek Dipak VD Shrestha Palikhe Nami N Vliagoftis Harissios H

Frontiers in medicine 20220729

PAR2, a receptor activated by serine proteases, has primarily pro-inflammatory roles in the airways and may play a role in asthma pathogenesis. PAR2 exerts its effects in the lungs through activation of a variety of airway cells, but also activation of circulating immune cells. There is evidence that PAR2 expression increases in asthma and other inflammatory diseases, although the regulation of PAR2 expression is not fully understood. Here we review th ...[more]

PMID: 35966869

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Project description:IntroductionDespite the current standard of care, patients with cardiovascular disease remain at a high risk for recurrent events. Inhibition of thrombin-mediated platelet activation through protease-activated receptor-1 antagonism may provide reductions in atherosclerotic disease beyond those achievable with the current standard of care.ObjectiveOur primary objective is to evaluate the clinical literature regarding the role of vorapaxar (Zontivity™) in the reduction of cardiovascular events in patients with a history of myocardial infarction and peripheral artery disease. In particular, we focus on the potential future directions for protease-activating receptor antagonists in the treatment of a broad range of atherosclerotic diseases.Data sourcesA literature search of PubMed and EBSCO was conducted to identify randomized clinical trials from August 2005 to June 2016 using the search terms: 'vorapaxar', 'SCH 530348', 'protease-activated receptor-1 antagonist', and 'Zontivity™'. Bibliographies were searched and additional resources were obtained.ResultsVorapaxar is a first-in-class, protease-activated receptor-1 antagonist. The Thrombin Receptor Antagonist for Clinical Event Reduction (TRACER) trial did not demonstrate a significant reduction in a broad primary composite endpoint. However, the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P-TIMI 50) trial examined a more traditional composite endpoint and found a significant benefit with vorapaxar. Vorapaxar significantly increased bleeding compared with standard care. Ongoing trials will help define the role of vorapaxar in patients with peripheral arterial disease, patients with diabetes mellitus, and other important subgroups. The use of multivariate modeling may enable the identification of subgroups with maximal benefit and minimal harm from vorapaxar.ConclusionVorapaxar provides clinicians with a novel mechanism of action to further reduce the burden of ischemic heart disease. Identification of patients with a high ischemic risk and low bleeding risk would enable clinicians to maximize the utility of this unique agent.

Dataset Information

Protease-activated receptor-2: Role in asthma pathogenesis and utility as a biomarker of disease severity.

Publications

Protease-activated receptor-2: Role in asthma pathogenesis and utility as a biomarker of disease severity.

Similar Datasets

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