# Plasma Sphingolipids and Subclinical and Clinical Cardiovascular Disease

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $692,708

## Abstract

ABSTRACT
Identification of novel modifiable factors associated with cardiac remodeling may lead to new
therapeutic approaches and opportunities for early prevention of heart failure. We recently reported
from data observed in the Cardiovascular Health Study (CHS), a prospective study of older adults, that
plasma ceramides (Cer) and sphingomyelins (SM) were associated with risk of incident heart failure,
but the associations of Cer and SM species with the saturated fatty acid 16:0 (16 carbons:0 double
bond) differed from the associations of species with the fatty acids 20:0, 22:0 or 24:0. The main
objectives of this current application are to probe the mechanistic underpinnings of the observed
association of Cer and SM with heart failure. Specifically, we aim to examine whether plasma Cer and
SM species with the fatty acids 16:0, 20:0, 22:0 and 24:0 are associated with changes over time in
cardiac imaging measures of hypertrophy (Aim 1a); and to examine the associations of Cer and SM
species with cardiac imaging measures of fibrosis (Aim 1b). Furthermore, we will determine metabolic
and transcriptional effects of altering levels of Cer and SM species in primary human ventricular
cardiomyocytes (Aim 2). We will extend the CHS findings on Cer and SM and heart failure to four
race/ethnic groups in MESA (Multi-Ethnic Study of Atherosclerosis), and we will gain evidence of
causality using Mendelian Randomization analyses (Aim 3). In addition, we will identify life-style and
other factors that influence changes in Cer and SM levels over time using repeat measurements, to
gain information for future prevention efforts (Aim 4). To address the study aims, we will measure Cer
and SM in 5,000 existing plasma samples in MESA, including 4000 baseline samples and 1000
repeats; we will use existing Cer and SM measurements in CHS and obtain new Cer and SM
measurements in 1000 samples in CHS; and we will conduct targeted experiments in cardiomyocytes.
The study will take advantage of existing, high quality cardiac magnetic resonance (CMR) data at two
time points, and gadolinium enhanced CMR imaging in MESA; existing Cer and SM data at one time
point in CHS; follow-up information, genetics data and extensive covariate data in both MESA and
CHS. This comprehensive project leverages two large, independent cohorts and targeted in vitro
experimentation in human cardiomyocytes to systematically define and validate the role of Cer and SM
in the progression to heart failure. Its successful completion will bring new insights into mechanisms
and processes critical in the early stages of cardiac failure and can help direct future novel drug targets
and prevention efforts.

## Key facts

- **NIH application ID:** 10201737
- **Project number:** 5R01HL146499-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Rozenn Lemaitre
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $692,708
- **Award type:** 5
- **Project period:** 2020-06-24 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201737

## Citation

> US National Institutes of Health, RePORTER application 10201737, Plasma Sphingolipids and Subclinical and Clinical Cardiovascular Disease (5R01HL146499-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201737. Licensed CC0.

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