Evidence map›Paper›PMID 41944007›Full record

ArticleCirculation2026

Olfactory Receptor Activation Reduces Platelet Reactivity and Arterial Thrombosis Through Actin Cytoskeleton Remodeling.

Anu Aggarwal, Vara Prasad V N Josyula, Nancy Wang, Moua Yang, Young Jun Shim, Quinn P Kennedy, Reina Samuel, Naseer Sangwan, Suman Guntupalli, Matthew Godwin and 13 more

Abstract read
In one paragraph

Article in Circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Anu AggarwalDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0002-2357-3827
Vara Prasad V N JosyulaCenter for Therapeutics Discovery, Cleveland Clinic Research , Cleveland Clinic Foundation, OH (V.P.V.N.J., N.W., S.S.).
Nancy WangCenter for Therapeutics Discovery, Cleveland Clinic Research , Cleveland Clinic Foundation, OH (V.P.V.N.J., N.W., S.S.).ORCID 0009-0009-7926-1273
Moua YangDivision of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine and Bloodworks Northwest Research Institute, Seattle (M.Y., Q.P.K.).
Young Jun ShimDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0002-4955-9564
Quinn P KennedyDivision of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine and Bloodworks Northwest Research Institute, Seattle (M.Y., Q.P.K.).
Reina SamuelDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).
Naseer SangwanDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0002-2407-769X
Suman GuntupalliDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0009-0009-8733-6386
Matthew GodwinDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0002-8365-7985
Huijun Edelyn ParkDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0002-6642-3925
Mariya AliDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).
Courtney JenningsDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).
Bhairavi RajasekarSection of Vascular Medicine, Department of Cardiovascular Medine, Heart Vascular and Thoracic Institute, Cleveland Clinic Foundation, OH (B.R., A. S, S.J.C.).ORCID 0009-0006-4384-0132
Alliefair ScaliseSection of Vascular Medicine, Department of Cardiovascular Medine, Heart Vascular and Thoracic Institute, Cleveland Clinic Foundation, OH (B.R., A. S, S.J.C.).ORCID 0009-0002-3743-4366
Anthony R SloanDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0001-7994-3316
Justin D LathiaDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0003-3168-7290
Jessica GrondolskyDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).
Sarah M SchumacherDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0002-4941-7267
Shaun StaufferCenter for Therapeutics Discovery, Cleveland Clinic Research , Cleveland Clinic Foundation, OH (V.P.V.N.J., N.W., S.S.).
Keith R McCraeDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0001-7340-475X
Thomas M McIntyreDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0001-7802-5900
Scott J CameronDepartment of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic Foundation, OH (A.A., Y.J.S., R.S., N.S., S.G., M.G., H.E.P., M.A., C.J., A.R.S., J.D.L., J.G., S.M.S., K.R.M., T.M.M., S.J.C.).ORCID 0000-0002-9616-1540

Funding

The Cleveland Clinic Innovation AcceleratorU54HL119810 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI VINCE, D. GEOFFREY · 2013 to 2020
$14.4M
Platelets as Biosensors and Mediators of Aortic Aneurysm GrowthR01HL158801 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI CAMERON, SCOTT JAMES · 2021 to 2025
$2.5M
Hypertension augmented COVID-19 through renin-induced internalization of platelet-ACE2 / SARS-Cov-2 complexesR01HL158669 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS M · 2021 to 2024
$2.3M
Oxidative Cysteine Modification by Thiol Isomerases in Sickle Cell DiseaseR00HL164888 · NHLBI · BLOODWORKS · PI Moua Yang · 2024 to 2026
$747k
Platelets as therapeutic and diagnostic entity in fibromuscular dysplasiaK99HL181079 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI Anu Aggarwal · 2025 to 2026
$238k
NHLBI NIH HHS K99 HL181079NHLBI NIH HHS R00 HL164888NHLBI NIH HHS R01 HL158669NHLBI NIH HHS R01 HL158801NHLBI NIH HHS U54 HL119810
6 · The paper itself

Abstract

backgroundDespite antiplatelet therapy, some patients remain at high ischemic risk because of drug nonresponsiveness or high residual platelet reactivity. We aimed to target an orphan platelet GPCR (G protein-coupled receptor) from the OR (olfactory receptor) family as a novel antithrombotic strategy.

methodsUsing an engineered reporter cell line expressing human

resultsWe identified 6 OR2L13 (olfactory receptor family 2 subfamily L member 13)-specific agonists that suppressed platelet aggregation and α-granule exocytosis through multiple receptors, suggesting a shared downstream mediator. The lead agonist (CCF0054500) phosphorylated platelet HSP27 (heat shock protein 27), disrupting the actin cytoskeleton and reducing clot retraction (clot area, 70.6 versus 5.2;

conclusionsWe describe and characterize the first nonolfactory probe for the purpose of inhibiting platelet activation and thrombosis through downstream HSP27 in a comprehensive investigation using a first-of-its-kind platelet inhibitor targeting an orphan platelet GPCR.

Indexed as

Actin CytoskeletonBlood PlateletsPlatelet ActivationReceptors, OdorantThrombosisAnimalsFemaleHeat-Shock ProteinsHSP27 Heat-Shock ProteinsHumansMaleMiceMice, Inbred C57BLMolecular ChaperonesPlatelet AggregationPlatelet Aggregation InhibitorsHeat-Shock ProteinsHSP27 Heat-Shock ProteinsHSPB1 protein, humanMolecular ChaperonesPlatelet Aggregation InhibitorsReceptors, Odorantactinsblood plateletsheat-shock proteinsmyocardial infarctionreceptors, odorantthrombosis

Identifiers

PMID41944007
PMCPMC13236044

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.