Ex vivo effects of low dose delayed release rapamycin on agonist-induced platelet aggregation, activation and procoagulant platelet phenotypes in domestic cats.

Meg Shaverdian, Nghi Nguyen, Stuart Fitzgerald, Louise Grubb, Joshua A Stern, Ronald H L Li

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Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

6 authors.

Meg ShaverdianDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.

Nghi NguyenDepartment of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.

Stuart FitzgeraldTriviumVet, Waterford, Ireland.

Louise GrubbTriviumVet, Waterford, Ireland.

Joshua A SternDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.

Ronald H L LiDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. rhli2@ncsu.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cardiogenic arterial thromboembolism (CATE) is a complication of cardiac diseases with a high mortality rate. Despite anti-platelet drugs use, on-treatment recurrence rate remains high indicating a critical need to discover novel therapies. Studies in both humans and cats show that low dose delayed release rapamycin (LDDRR) can reduce the progression of left ventricular hypertrophy. However, its effect on platelets is unclear. In this study we assessed the ex vivo effects of LDDRR on platelet aggregation, alpha-granule secretion indicated by an increase in P-selectin, and procoagulant platelet phenotypes including loss of mitochondrial membrane potential (ΔΨm) and phosphatidylserine (PS) exposure. Cats were treated with 0.3 mg/kg LDDRR orally every 7 days for 4 consecutive weeks. Blood was collected at 3, 24 and 48 h after the last dose. While LDDRR had no effect on aggregation, it significantly decreased P-selectin expression in thrombin + COL (3 h), and ADP (24, 48 h) samples. LDDRR had protective effects on ΔΨm in all agonists at all times. PS exposure was reduced at 24 h in thrombin ± COL samples. Our study indicated that LDDRR in cats can safely modulate platelet activation, procoagulant phenotypes and tendency in varying degrees making it an effective candidate to prevent CATE.

Indexed as

Blood PlateletsPlatelet ActivationPlatelet AggregationSirolimusAnimalsBlood CoagulationCatsFemaleMaleMembrane Potential, MitochondrialPhenotypeP-SelectinThrombinP-SelectinSirolimusThrombinCardiogenic arterial thromboembolismHypertrophic cardiomyopathyMitochondrial membrane potentialPhosphatidylserineProcoagulant plateletsRapamycin

Identifiers

PMID41965408

DOI10.1038/s41598-026-46991-z

PMCPMC13221459

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LicenceCC BY-NC-ND

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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.