Variants of PEAR1 Are Associated With Outcome in Patients With ACS and Stable CAD Undergoing PCI

Stimpfle, Fabian; Bauer, Maike; Rath, Dominik; Schaeffeler, Elke; Schwab, Matthias; Gawaz, Meinrad; Winter, Stefan; Geisler, Tobias

doi:10.3389/fphar.2018.00490

Cited by 20 publications

(13 citation statements)

References 33 publications

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“…PEAR1, which triggers platelet aggregation, plays a very important role in platelet function. Genetic variants of PEAR1 are associated with cardiovascular events in patients undergoing PCI and treated with aspirin in combination with clopidogrel (Nie et al, 2018; Stimpfle et al, 2018; Yao et al, 2018). PON1 gene variations may be a risk factor of bleeding after aspirin and clopidogrel therapy (Lei et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The Management of Heavy Menstrual Bleeding After Percutaneous Coronary Intervention in a Woman of Reproductive Age

Shi

Zhu

et al. 2019

Front. Pharmacol.

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Heavy menstrual bleeding (HMB), previously known as menorrhagia, is in place with heavy flow and longer lasting days of bleeding during menstrual period, sequentially leading to anemia. We reported a rare case of HMB in a 33-year-old patient after percutaneous coronary intervention (PCI), who presented with acute coronary syndromes (ACS), uremia and systemic lupus erythematosus before PCI. This patient received three times of hemodialysis weekly (Monday, Wednesday, and Friday). On the next day after PCI, this patient began to have menstruation. On the fifth day of menstruation, the patient complained of HMB and physical discomfort, with an urgent need for consultation of gynecologist. After gynecologist consultation, this patient was under oxytocin treatment. However, 2 days of oxytocin treatment did not significantly improve HMB. Afterward, the menstrual volume of patients was significantly reduced on eighth day of menstruation after once therapy of testosterone propionate and norethindrone. Regarding the reasons of HMB, heparin in hemodialysis and antiplatelet drugs utilized (aspirin and clopidogrel) after PCI may be contributors to the HMB. In addition, uterine myoma, cervical canal cyst, renal insufficiency and CYP2C19∗2 heterozygous are also possible contributors to HMB. There is no such case of whom had HMB in reproductive age with ACS, uremia and systemic lupus erythematosus under hemodialysis and antiplatelet therapy. More clinical safety data on HMB of reproductive age women who are under antithrombotic therapy are required.

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Section: Discussionmentioning

confidence: 99%

The Management of Heavy Menstrual Bleeding After Percutaneous Coronary Intervention in a Woman of Reproductive Age

Shi

Zhu

et al. 2019

Front. Pharmacol.

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“…Our co-localization results with platelet eQTLs are consistent with a model that a single, common causal variant explains the platelet reactivity signal. While results of previous association studies on PEAR1 variants and coronary disease are mixed [18][19][20][21] , UK BioBank 22 data supports an association ( Supplementary Table 6).…”

mentioning

confidence: 81%

Genome Sequencing Unveils a New Regulatory Landscape of Platelet Reactivity

Keramati

Chen

Rodriguez

et al. 2019

Preprint

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Exaggerated platelet aggregation at the site of vascular injury is the underlying pathophysiology of thrombotic diseases. Here, we conduct the largest whole genome sequencing (WGS) effort to uncover the genetic determinants of platelet aggregation. Leveraging 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) individuals deeply phenotyped for platelet aggregation, we identify 18 loci using single-variant approaches. This includes the novel RGS18 locus encoding a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with eQTL signatures for RGS18 expression in platelets. A gene-based approach focusing on deleterious coding variants identifies the SVEP1 gene, previously shown to be associated with coronary artery disease, as a novel determinant of platelet aggregation. Finally, in an integrative approach leveraging epigenetic data on megakaryocytes, we find strong association between rare variants mapping to a super enhancer region for PEAR1. This is a novel finding implicating the importance of rare variants with regulatory potential in a previously documented GWASidentified locus.

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“…Some of the common variants of PEAR1 and their correlations with platelet function and disease identified by genome wide association studies (GWAS) are summarized in Table 1 [16][17][18][19][20][21]. Many of the single nucleotide variants (SNVs) are found in introns, which could lead to alternative splicing of PEAR1 but also regulation of other distant genes.…”

Section: Pear1 In Cardiovascular Disease: Gwas Studiesmentioning

confidence: 99%

“…The primary associations of the SNVs in PEAR1 is with cardiovascular diseases, and include an increase in risk for coronary artery aneurysm in patients with Kawasaki disease [17], and following percutaneous coronary intervention treatment for coronary artery disease and acute coronary syndromes [18]. An association with pulmonary thromboembolism in a Chinese family of three generations has also been reported but further case studies are needed to confirm this association [21].…”

Section: Pear1 In Cardiovascular Disease: Gwas Studiesmentioning

confidence: 99%

Is the endogenous ligand for PEAR1 a proteoglycan: clues from the sea

et al. 2020

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Platelet Endothelial Aggregation Receptor 1 (PEAR1) is an orphan receptor of unknown function which mediates powerful activation of platelets and endothelial cells in response to crosslinking by antibodies and sulfated polysaccharides belonging to the dextran and fucoidan families. PEAR1 is a single transmembrane protein composed of 15 epidermal growth factor-like repeat sequences and with a conserved binding motif, YXXM, which when phosphorylated binds to phosphoinositide 3-kinase (PI3K). The 13 th of the repeats has a heparin-binding sequence that is the site of interaction with the sulfated fucoidans and the only known endogenous ligand FcRI. Crosslinking of PEAR1 drives Src family kinase phosphorylation of the cytosolic tail leading to binding and activation of PI3K. In this Opinion Article, we summarise the literature on PEAR1 expression, structure and signalling, and the search for further endogenous ligands. We highlight one article in which phosphorylation of a 150 kDa platelet protein by heparin-containing ligands has been reported and propose that PEAR1 is a receptor for one or more glycosaminoglycan-conjugated proteins (proteoglycans). The up-regulation of PEAR1 at sites of inflammation in the vasculature and its role in angiogenesis suggests a role in the interplay of inflammation, platelets, coagulation and thromboinflammation. We speculate that this may explain the link between single nucleotide variants in PEAR1 and cardiovascular disease.

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Variants of PEAR1 Are Associated With Outcome in Patients With ACS and Stable CAD Undergoing PCI

Cited by 20 publications

References 33 publications

The Management of Heavy Menstrual Bleeding After Percutaneous Coronary Intervention in a Woman of Reproductive Age

The Management of Heavy Menstrual Bleeding After Percutaneous Coronary Intervention in a Woman of Reproductive Age

Genome Sequencing Unveils a New Regulatory Landscape of Platelet Reactivity

Is the endogenous ligand for PEAR1 a proteoglycan: clues from the sea

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