# Circulating microparticle effects on phenotypically distinct pulmonary endothelium

> **NIH NIH R01** · UNIVERSITY OF SOUTH ALABAMA · 2020 · $378,750

## Abstract

PROJECT SUMMARY
Pulmonary artery and capillary endothelial cells are structurally and functionally heterogeneous in multiple
ways including their inflammatory response. In pulmonary arterial hypertension (PAH), CD68-positive
monocytes accumulate around arterioles as opposed to migrating into the alveolar space as they do in acute
lung injury. Further, inflammatory infiltrates are a feature of late-stage disease, are localized to small arterioles,
and are not as observable in the early stages of PAH. The contributions of the inflammatory cell infiltrates
include release of growth factors and further inflammatory stimuli. The precise mechanisms that influence the
temporal recruitment of inflammatory cells to the perivascular space in select size vessels and the influence of
the phenotypically distinct endothelium remain unknown. Microparticle signaling within phenotypically distinct
endothelium has not been considered and could have significant implications toward adhesion molecule
expression. We found that microparticles from late-stage PAH rats were endocytosed and localized to the
perinuclear space in pulmonary artery endothelial cells (PAECs), induced adhesion molecule expression, and
promoted leukocyte adhesion. However, none of these events occurred in pulmonary microvascular
endothelium (PMVECs) with the same treatment. Further, microparticles isolated from the circulation of early-
stage PAH rats had none of these effects on either cell type. To determine the mechanism of microparticle
signaling in the PAECs we examined Rab proteins responsible for vesicle trafficking and intracellular
localization. RNAseq analysis and RT-PCR of PAECs and PMVECs revealed Rab36 is expressed only in the
PAECs. Rab36 is a newly identified RabGTPase responsible for retrograde transport of vesicles to the Golgi
and nucleus. Based on these data this proposal tests the overall HYPOTHESIS that late-stage
microparticles, circulating in PAH, increase adhesion molecule expression selectively in the
pulmonary arteries dependent on Rab36. SPECIFIC AIMS test the hypotheses that circulating
microparticles obtained from late-stage, but not early-stage PAH: 1. Stimulate expression and activity of
adhesion molecules selectively in the pulmonary artery. 2. Are dependent on Rab36 for uptake and
subcellular localization in the pulmonary artery.

## Key facts

- **NIH application ID:** 9991632
- **Project number:** 5R01HL133066-04
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **Principal Investigator:** Natalie Norwood Bauer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,750
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991632

## Citation

> US National Institutes of Health, RePORTER application 9991632, Circulating microparticle effects on phenotypically distinct pulmonary endothelium (5R01HL133066-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991632. Licensed CC0.

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