# Contributions of Myeloid Metabolism to Diastolic Dysfunction

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $514,716

## Abstract

Thorp Project Summary Abstract
Diastolic dysfunction (DD) and Heart failure with Preserved Ejection Fraction (HFpEF) are
significant and hetetogenous causes of morbidity and mortality with few effective therapeutic
strategies. Increased understanding of HFpEF has been earmarked as a NIH research priority.
Two risk factors, fat and hypertension, are commonly found in cardiometabolic HFpEF patients,
and both independently associate with inflammation and DD. The extent of inflammation is a
critical determinant of the degree of cardiac fibrosis and myocardial stress that likely contributes
to impaired cardiac performance. As such, the resolution of inflmammation has the potential to
ameliorate myocardial pathophysiology. In this context, inflammatory immunometabolic
signaling has been linked with to the progression of disease, yet little is known with respect to
how immune metabolism regulates DD. This is particuarly true for myeloid cells and especially
the macrophage, in which immuonometabolic contriubtions to DD are either unknown or vague.
Our preliminary data point to signifcant mitochondrial stress in macrophages during DD. This is
an opportunity to combine improved basic understanding of basic cellular mechanisms with the
revealing on potential new metabolic therapeutic targets. In our first experimental Aim, we will
test the causal associations of myeloid lipid and mitochondrial metabolic pathways during
experimental DD. Aim II will elucidate cell-intrinsic immunometabolic macrophage signaling
networks that regulate pathways of inflammatory acceleration during DD-associated pathology.
Aim III will test the therapeutic proof of principle and clinical relevance of myeloid cell
metabolism during DD. Our Aims will leverage newly generated and cutting-edge experimental
tools and approaches. Taken together, these studies will provide new insight into the underlying
inflammatory mechanisms and therapeutic immune targets of DD and immunometabolic
signaling.

## Key facts

- **NIH application ID:** 10464077
- **Project number:** 1R01HL159964-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Edward Benjamin Thorp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $514,716
- **Award type:** 1
- **Project period:** 2022-08-23 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464077

## Citation

> US National Institutes of Health, RePORTER application 10464077, Contributions of Myeloid Metabolism to Diastolic Dysfunction (1R01HL159964-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10464077. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*