# Advanced CV imaging and immunophenotyping to study coronary vascular health in psoriasis

> **NIH NIH K23** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $191,920

## Abstract

Project Summary/Abstract
Psoriasis is highly linked to cardiovascular disease (CVD), including myocardial infarction (MI), heart failure and
CV mortality. An increased prevalence of CV risk factors in these patients only partially accounts for this
enhanced clinical risk. Although systemic inflammation is thought to be a key mediator of the onset and
progression of these cardiometabolic abnormalities, the excess CV risk conferred by psoriatic disease remains
understudied. We will use novel multi-modality cardiac imaging to quantify abnormalities in vascular health, and
cardiac structure and function and assess the association with cellular immunophenotype. The central
hypothesis of this study is that reducing inflammation with tildrakizumab, an FDA approved therapy for psoriasis
that inhibits the IL-23 and Th17 pathway of inflammation, will quantitatively improve myocardial blood flow and
coronary flow reserve (CFR) as measured by positron emission tomography (PET) over 6 months in patients
with moderate-severe psoriasis disease and enhanced CV risk. In so doing, improvement in coronary
vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics,
and ultimately, symptoms and prognosis. We propose to use two state-of-the-art techniques, quantitative
perfusion PET imaging and cellular immunophenotyping by single cell analysis [single cell RNA-seq, cellular
indexing of transcriptomes and epitopes (CITE)-seq] of peripheral blood mononuclear cells, combined with
echocardiography. In Specific Aim 1, we will evaluate whether tildrakizumab therapy will (1) improve coronary
vascular function based on CFR, (2) improve myocardial mechanics, and (3) whether this functional improvement
will be correlated with the change in CFR after 6 months of treatment. In Specific Aim 2, we will evaluate the
relationship between cellular immunophenotype and coronary vasomotor dysfunction and myocardial
mechanics, at baseline and after therapy with tildrakizumab for 6 months. The overarching goal of this proposal
is to use physiologic imaging techniques already available as part of routine clinical care, and novel cellular
immunophenotyping to investigate mechanisms linking psoriatic disease and inflammation to coronary vascular
health and cardiac structure and function. This study will address an unmet and needed clinical translation in
psoriatic disease. This research will be accomplished in the setting of a comprehensive career development
program designed to provide the candidate, an early career investigator with training in CV medicine and CV
imaging, with the skills needed to become an independent physician-scientist in CV medicine. Her long-term
career goal is to be an independent scientific investigator, integrating immunology with cardiovascular imaging
to better define the role of systemic inflammation in cardiovascular pathophysiology, and ultimately inform future
therapeutic trials. An outstanding mentoring tea...

## Key facts

- **NIH application ID:** 10282761
- **Project number:** 1K23HL159276-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Brittany nicole Weber
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,920
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10282761

## Citation

> US National Institutes of Health, RePORTER application 10282761, Advanced CV imaging and immunophenotyping to study coronary vascular health in psoriasis (1K23HL159276-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10282761. Licensed CC0.

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