# The Impact of Shear Stress on Aquaporin 1 Expression in the Pulmonary Endothelium

> **NIH NIH F32** · JOHNS HOPKINS UNIVERSITY · 2024 · $83,932

## Abstract

PROJECT SUMMARY
Pulmonary endothelial cells (ECs) are in direct contact with laminar blood flow, resulting in exposure to shear
stress. Normal blood flow provides a physiologic degree of shear stress at which ECs achieve quiescence.
Pathologic changes in shear stress can occur in several conditions ranging from pulmonary embolism, where
shear stress acutely decreases due to vessel occlusion, to pulmonary hypertension (PH), where shear stress in
the distal arteries increases due to luminal narrowing. These disease entities carry considerable morbidity and
mortality despite available therapeutics. The biochemical derangements that occur when shear stress is altered
are not well-characterized, and elucidating these pathways may provide novel insight into potential therapeutic
targets to prevent long-term dysfunction of ECs. In vitro culture of ECs is often performed under static conditions,
leading to underappreciation of the effects of physiologic shear stress on normal cellular function as well as the
biochemical and functional impact of shear perturbations. Aquaporin 1 (AQP1), a ubiquitous protein that forms
water channels, is known to be expressed in vivo in the pulmonary endothelium, but we noted that AQP1
expression is not observed in human lung microvascular endothelial cells (hLMVECs) grown in static cell culture.
My preliminary data show restored AQP1 expression in cultured hLMVECs with exposure to physiologic shear
stress, suggesting a critical role of shear stress in dynamically regulating AQP1 expression. Increased AQP1 has
recently been linked to important cellular functions, including angiogenesis and proliferation in certain
malignancies, as well as contributing to vascular remodeling through apoptosis resistance and hyperproliferation
in the ECs from rat models of PH. Regulation of AQP1 is not well-described in hLMVECs but is calcium-
dependent in pulmonary vascular smooth muscle cells. Aim 1 of this proposal is designed to elucidate the
biochemical signaling that occurs in response to changes in shear stress. In preliminary data, I show intracellular
calcium levels increase in response to increased shear stress. I seek to define this signaling pathway focusing
on the role of activation of the membrane ion channel, TRPV4, which can increase calcium influx in ECs in
response to mechanical stimuli, in regulating AQP1 levels. Aim 2 will explore the functional outcome of changes
in AQP1 expression in response to varying degrees of shear stress, focusing on apoptosis and proliferation.
Techniques utilized will include but are not limited to cell culture under shear stress, ratiometric calcium
measurement, protein and mRNA measurement, immunofluorescence microscopy, and measures of apoptosis
and proliferation. Completion of this project will provide novel insight into the impact of shear stress on EC
function, and how derangements in shear stress may alter cell signaling and cell growth and survival. The skills
acquired in the design and e...

## Key facts

- **NIH application ID:** 10998236
- **Project number:** 1F32HL176197-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Michael Croglio
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $83,932
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998236

## Citation

> US National Institutes of Health, RePORTER application 10998236, The Impact of Shear Stress on Aquaporin 1 Expression in the Pulmonary Endothelium (1F32HL176197-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10998236. Licensed CC0.

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