# Atherothrombosis in JAK2V617F clonal hematopoiesis

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $674,641

## Abstract

Project Summary/Abstract
Clonal hematopoiesis (CH) occurs when somatic mutations provide a fitness advantage to
hematopoietic stem and progenitor cells, leading to clonal expansion of mutant blood cells. CH is
highly prevalent in the elderly and has emerged as a major independent risk factor for
atherosclerotic cardiovascular disease (CVD). Among the common genetic variants of CH,
individuals with JAK2V617F CH have an outstanding risk of myocardial infarction and of venous and
arterial thrombosis. JAK2V617F variants are present in 3-4% of a general European population and
are associated with increased thrombotic risk at very low allele burden. There is no approved
therapy for this risk. We have demonstrated increased atherosclerosis in chimeric mice that model
JAK2V617F CH, involving elevated inflammasome activation and IL-1β production. While
atherosclerosis in CH has been intensively studied, the impact and mechanisms of CH driven
atherothrombosis have not been extensively investigated. Our preliminary studies have shown
accelerated atherothrombosis in Jak2VF CH models. While our studies suggest the underlying
importance of JAK2V617F platelets, myeloid cells and erythrocytes as well as the cross-talk from
mutant to wild type cells in atherosclerosis and atherothrombosis, the relative importance of
different blood cell types and of cross-talk between cell types need to be more rigorously assessed.
We propose to use novel mouse models to interrogate the role of different blood cells and the
relevant pathways and mechanisms involved in accelerated atherosclerosis and
atherothrombosis in JAK2V617F CH. Elucidation of the different proposed mechanisms may lead
to the development of precision therapeutic approaches to reduce atherosclerotic and
atherothrombotic risk in JAK2VF CH.

## Key facts

- **NIH application ID:** 10882597
- **Project number:** 2R01HL148071-05A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** NAN WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $674,641
- **Award type:** 2
- **Project period:** 2019-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882597

## Citation

> US National Institutes of Health, RePORTER application 10882597, Atherothrombosis in JAK2V617F clonal hematopoiesis (2R01HL148071-05A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10882597. Licensed CC0.

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