# Defining the cellular and molecular mechanisms driving neointimal lesion growth in pulmonary hypertension

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $668,323

## Abstract

Project Summary/Abstract
Pulmonary hypertension (PH) is a fatal disease of the pulmonary arteries with few supportive
therapies and no cure. In PH, occlusive `neointimal lesions' grow within small pulmonary
arteries and narrow vessel lumens, increasing pulmonary vascular resistance, ultimately
resulting in right heart failure and death. Available PH therapies are vasodilators that do not
target neointimal growth and neither prevent progression nor reverse disease. Understanding
the biology of neointimal lesion growth – which cells are responsible for lesion expansion, and
the pathways that control their proliferation – is key to the development of more effective
therapies for pulmonary hypertension. In preliminary studies we find that proliferating neointima
cells are adjacent to artery endothelial cells and have distinct gene expression that distinguishes
them from cells located away from the endothelium. We hypothesize that a molecularly defined
subset of neointimal cells located adjacent to the endothelium is the proliferating fraction that
expands neointimal lesions, and that signals from the endothelium regulate lesion growth.
Specific Aims: (1) Using proliferation tracking, genetic lineage tracing and ablation, identify and
molecularly characterize the subset of neointimal cells whose proliferation is responsible for
lesion growth. (2) Through bioinformatic analysis of single cell transcription in neointima and
artery endothelial cells from mouse and human, identify candidate signals driving neointimal
proliferation in PH and the core disease mechanisms shared between mouse and human. (3)
Test the ability of a key candidate driver of neointimal proliferation for a role in lesion growth in
multiple PH models. Here, by utilizing cutting edge technologies, genetics, and single cell
approaches across multiple model systems, these experiments will provide a granular
understanding of the cells and signals driving neointimal lesion expansion, adding substantially
to the current knowledge surrounding the pathology of vascular remodeling in PH, findings we
hope will ultimately lead to neointima-blocking treatment options.

## Key facts

- **NIH application ID:** 10594934
- **Project number:** 5R01HL163013-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Maya Elise Kumar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $668,323
- **Award type:** 5
- **Project period:** 2022-03-20 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10594934

## Citation

> US National Institutes of Health, RePORTER application 10594934, Defining the cellular and molecular mechanisms driving neointimal lesion growth in pulmonary hypertension (5R01HL163013-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10594934. Licensed CC0.

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