# Platelet Activity and Vascular Health in Systemic Lupus Erythematosus

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $798,104

## Abstract

PROJECTSUMMARY/ABSTRACT
Systemic lupus erythematosus (SLE) is a complex autoimmune disease that poses several challenges to
the clinician, including heterogeneity of presentation, undulating course, and a significantly elevated risk for
vascular dysfunction and premature cardiovascular disease. Traditional risk factors are limited in their ability to
discriminate cardiovascular risk in patients with SLE. Platelets, which contain transcripts and the
necessary molecular machinery to conduct translation, are intercellular regulators of atherothrombosis,
vascular dysfunction, inflammation, and immune activation. Activated platelets can induce endothelial cells
and monocytes to produce inflammatory cytokines and chemokines resulting in vascular injury and
subsequent atherogenesis. Platelets have been understudied as a relevant contributor to vascular
dysfunction and premature cardiovascular disease in SLE.
We propose a complementary set of studies to fully evaluate the mechanistic role of platelets in patients
with SLE. The array of studies will include platelet activity measurements, coding and non-coding RNA
profiles, platelets as effector cells regulating endothelial cell and leukocyte activity in vitro, and
measurement of vascular health in vivo using brachial artery reactivity testing. The proposed approach
will include a cross sectional study of 200 SLE patients to cover the full spectrum of organ involvement and
disease activity. We will also enroll 50 age- sex- and race/ethnicity- matched disease controls. The study
hypotheses are that (1) platelet activity measurements and platelet-derived coding and noncoding RNA are
significantly influenced by disease activity and clinical phenotype, (2) SLE platelets will induce inflammatory,
thrombogenic, and adhesive gene expression and consequent reactivity in endothelial cells,
monocytes/macrophages, and vascular smooth muscle cells, and (3) SLE platelet phenotype and
transcriptome will significantly associate with impaired vascular function. Longitudinal follow-up in 50
patients representative of both active and quiescent disease will allow us to ascertain whether biologic
readouts track with a specific subset of patients and whether the readouts change over time.
This study will provide novel data to address existing gaps in knowledge regarding the association
between platelet activity measurements, the platelet transcriptome, and platelets as effector cells and
vascular health across the clinical spectrum of SLE. This study will ascertain whether there is a unique
platelet RNA expression profile in SLE with increased platelet activity and/or with impaired vascular health.
Data obtained from this study will identify SLE patients at increased risk for vascular dysfunction and
cardiovascular disease by investigating a potentially modifiable risk factor. These data should provide
insight into the molecular mechanisms regulating platelet activity in SLE, novel diagnostic tests for risk
stratification, an...

## Key facts

- **NIH application ID:** 9842004
- **Project number:** 5R01HL139909-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jeffrey S Berger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $798,104
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842004

## Citation

> US National Institutes of Health, RePORTER application 9842004, Platelet Activity and Vascular Health in Systemic Lupus Erythematosus (5R01HL139909-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9842004. Licensed CC0.

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