# Proteomic signatures to identify  pathways underlying the progression to  heart failure

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $929,711

## Abstract

Heart failure (HF) disproportionately affects the elderly who predominantly develop HF with preserved left
ventricular ejection fraction (HFpEF). Neurohormonal blockade has not proven efficacious for HFpEF, and no
disease-specific therapy currently exists. There is an urgent need for novel targetable pathways, and
basic/translational data implicate systemic inflammation as a potential unexploited therapeutic target,
although human data is limited. The objective of this application is to define the contributions of inflammatory
pathways to, and identify novel causal pathways for, the development of cardiac dysfunction and overt HF in
the elderly. The central hypothesis is that specific inflammatory and neurohormonal pathways will
differentially predict progressive LV dysfunction and incident HF phenotype (HFpEF vs HFrEF) in late life,
and that detailed longitudinal proteomic and phenotypic data will allow for discovery of novel biologic
pathways and prognostic risk markers for HF. Aptamer-based proteomics provide precise quantification of
4,931 circulating proteins and unprecedented profiling of relevant inflammatory and non-inflammatory
pathways. Employing rigorous epidemiologic approaches, we will combine large-scale proteomics with detailed
longitudinal cardiovascular phenotyping (echo, pulse wave velocity) and prospective HF adjudication in the
largely biracial Atherosclerosis Risk in Communities (ARIC) cohort to address the following specific aims: 1) To
identify individual circulating proteins and protein networks that predict incident HF and HF phenotype
(HFpEF vs HFrEF); 2) To determine proteins and protein networks associated with longitudinal worsening of
LV diastolic and systolic function; 3) To identify candidate proteins and protein networks most likely to be
mediators of progressive LV dysfunction and HF using genomic data. The contributions of the proposed
research will be to clarify the role of inflammatory – relative to neurohormonal – pathways for HF
development and to discover novel mediators of HF in late life. These contributions will be significant because
by determining the importance of pathways targeted by several existing agents, our findings could rapidly
translate into novel preventative interventions for HF – an essential step to decrease HF-associated morbidity
and mortality. This research proposal is fundamentally innovative in: (1) focusing on large-scale circulating
proteomics to understand HFpEF pathobiology, with simultaneous assessment of inflammatory,
neurohormonal, and novel pathways in a cohort at risk for HFpEF to prevent HF development; (2) integrating
proteomic and genomic data to identify candidate proteins and pathways that are HF risk mediators as
opposed to risk markers; and (3) assessing novel antecedents to HFpEF beyond hypertrophy and diastolic
dysfunction, including impaired LV strain, pulmonary vascular dysfunction, and RV dysfunction. This project
is expected to provide an original, integrated un...

## Key facts

- **NIH application ID:** 9973983
- **Project number:** 1R01HL148218-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Amil M Shah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $929,711
- **Award type:** 1
- **Project period:** 2020-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973983

## Citation

> US National Institutes of Health, RePORTER application 9973983, Proteomic signatures to identify  pathways underlying the progression to  heart failure (1R01HL148218-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9973983. Licensed CC0.

---

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