# Systemic sclerosis (SSc) vasculopathy: Improved clinical monitoring and treatment

> **NIH VA I01** · VA SALT LAKE CITY HEALTHCARE SYSTEM · 2021 · —

## Abstract

Systemic sclerosis (SSc; scleroderma) is a complex autoimmune disease without a cure or an effective
therapy for the many devastating aspects of disease. Mouse models do not recapitulate all features of SSc,
mandating human studies for understanding this complex pathogenesis. The median survival is ~11 years after
SSc diagnosis and the estimated national hospital costs related to SSc exceed 275 million yearly. SSc affects 250
per 1 million people in the US, with a ~3-4 time greater prevalence among Veteran’s Health Administration
patients. The pathogenesis of SSc is characterized by immunological abnormalities, vascular changes, notably in
the microvasculature, and fibrosis, yet both the cause and effect of these mechanisms within the gastrointestinal
tract (GIT), which is the most common extra-cutaneous organ system damaged in SSc, is unknown.
 Our previous work supported by I01 CX002111-01 “Systemic sclerosis (SSc) vasculopathy: Improved
clinical monitoring and treatment” discovered that that both large artery (i.e., brachial artery), as well as
microvascular (i.e., arterioles and capillaries) endothelial dysfunction is a critical feature of SSc. A dysfunctional
endothelium leads to increased vascular permeability, greater tissue immune cell infiltration, blunted angiogenic
capacity and impaired vascular reactivity and tissue blood flow. While we showed that acutely we could improve
this vascular dysfunction, clinical interventions are limited by trial design issues and are greatly improved by
models that specifically study the mechanism of disease. We identified a novel method for quantifying
microvascular change in the oral cavity (sublingual videomicroscopy) that correlates to GIT symptoms in SSc.
This sublingual videomicroscope measures the glycocalyx, which maintains homeostasis of the vasculature,
including controlling vascular permeability and microvascular tone, preventing microvascular thrombosis, and
regulating leukocyte adhesion.
 In the first specific aim of our proposed study, we will perform a natural history study of the glycocalyx,
its relation to GIT patient reported outcomes (PRO) and end-stage vasculopathy features, including digital ulcers
(DU), pulmonary hypertension (PH), scleroderma renal crisis (SRC), calcinosis, and telangiectases. In the second
specific aim of the proposed study, we will develop a novel model to further study these end-stage vasculopathy
features (DU, PH, SRC, calcinosis, telangiectases, and severe GIT symptoms) in Veterans with SSc. We will
generate endothelial cells (EC) from inducible pluripotential stem cells (iPSC) created from their blood and age-
frequency and sex matched healthy controls. The main research objective of this project is to build upon our
current clinical research program for our Veterans with SSc that has identified important in vivo aspects of SSc
vasculopathy and its relation to PRO. The over-arching goal of this project renewal is to define SSc-GIT
vasculopathy through serial ...

## Key facts

- **NIH application ID:** 10252115
- **Project number:** 1I01CX002111-01A2
- **Recipient organization:** VA SALT LAKE CITY HEALTHCARE SYSTEM
- **Principal Investigator:** Tracy Minan Frech
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10252115

## Citation

> US National Institutes of Health, RePORTER application 10252115, Systemic sclerosis (SSc) vasculopathy: Improved clinical monitoring and treatment (1I01CX002111-01A2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10252115. Licensed CC0.

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