# Altered High-Density Lipoprotein function in Patients with Idiopathic Inflammatory Myopathies

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $181,980

## Abstract

PROJECT SUMMARY/ABSTRACT
Damage to the vascular endothelium is responsible for cardiovascular disease, which is the leading cause of
mortality in patients with autoimmune diseases. In idiopathic inflammatory myopathies (IIM), this process is
particularly relevant as vascular damage is implicated in the disease pathogenesis as well as its associated
major organ complication, interstitial lung disease (IIM-ILD). However, the precise mechanisms of ongoing
endothelial activation and vascular damage in IIM are currently not well understood. The proposed research
addresses a critical knowledge gap regarding the pathogenesis of vascular injury in IIM and IIM-ILD by
investigating a novel mechanism for perpetuation of vascular damage mediated by dysfunctional high-density
lipoproteins (HDL). HDL normally protects vascular endothelium from damage, but under certain inflammatory
states, HDL may lose its anti-inflammatory properties and become a dysfunctional, pro-inflammatory particle
that promotes endothelial cell damage. Our recent work demonstrates that the antioxidant function of HDL and
HDL-associated antioxidant enzyme paraoxonase-1(PON1) activity are impaired in patients with IIM, and
correlate with more active disease. The gut microbiome has shown strong associations with HDL and is known
to impact cardiovascular and lung health. Our preliminary results of the gut microbiome in IIM and controls
show a link between microbial composition and PON1 activity. We hypothesize that changes in HDL-
associated enzymes and proteins, pro-inflammatory bioactive mediators (BLM) and the gut microbiome result
in dysfunctional HDL, leading to the perpetuation of vascular endothelial damage and ultimately increased IIM
disease burden. We will use a longitudinal IIM cohort and comprehensive assessments of HDL function to
study the following specific aims: (1) evaluate the association between abnormal HDL function and
vasculopathy; (2) determine whether changes in abnormal HDL function over time correlate with disease
burden; and (3) examine the association of gut microbiome with HDL function and disease burden. The project
will be conducted at the University of California Los Angeles (UCLA) with the support of a multidisciplinary
team of mentors comprised of nationally recognized experts, and numerous resources of a major academic
institution, including graduate courses, core facilities, and career development seminars. Completion of the
proposed project and training plan will facilitate advanced training in the following areas: (1) microbiome study
design, data collection sequencing and analysis; (2) laboratory techniques and statistical analysis methods for
complex biomarker panels; and (3) disease outcome measures in IIM, including a quantitative imaging scoring
system in IIM-ILD. Training in these areas will provide a foundation to achieve my long-term goal, to be an
independent physician-scientist combining clinical, experimental and computational approaches to d...

## Key facts

- **NIH application ID:** 10739224
- **Project number:** 1K23AR081423-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Sangmee Bae
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $181,980
- **Award type:** 1
- **Project period:** 2023-09-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10739224

## Citation

> US National Institutes of Health, RePORTER application 10739224, Altered High-Density Lipoprotein function in Patients with Idiopathic Inflammatory Myopathies (1K23AR081423-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10739224. Licensed CC0.

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