# Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Calcification

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $118,449

## Abstract

ABSTRACT
This proposal describes a five-year mentored physician-scientist training program to characterize the
mechanobiology of endothelial-to-mesenchymal transition (EndMT) in cardiovascular calcification.
Cardiovascular calcification is a highly prevalent process whereby calcium mineral forms within the blood vessels
and heart tissue, and its presence is associated with an increased risk of morbidity and mortality. Despite
decades of research, there remains no effective medical therapy to treat this process. Recent work has
implicated EndMT in cardiovascular calcification. EndMT describes the phenomenon whereby endothelial cells
lining the lumen of the heart valves or blood vessels are stimulated to dedifferentiate into mesenchymal cells.
Subsequently, these mesenchymal cells are capable of differentiating into various lineages, including the
chondrogenic and osteogenic lineages that can promote calcification. While EndMT is a promising target for
therapeutic intervention in cardiovascular calcification, characterizing the EndMT process in experimental
studies can be challenging. Current methods to assess EndMT, such as genetic lineage tracing studies and
immunostaining detection of endothelial and mesenchymal marker expression, are labor-, resource-, and time-
intensive. Further, these methods are binary assessments of EndMT and do not capture an important aspect of
the process – its dynamic mechanical nature. Endothelial cells undergoing EndMT alter their cytoskeletal
mechanics, detach from their neighboring cells, and migrate into the interstitial space. Thus, their mechanical
properties, or “mechanophenotype,” during EndMT are likely dynamic, but have not been previously explored.
In this proposal, we outline our aims to characterize the mechanophenotypes of EndMT, with the hope of
developing novel, high-throughput platforms to more rapidly identify possible therapeutic targets for EndMT-
related disease, including cardiovascular calcification. Further, the accompanying mentored career development
training plan will allow the candidate to develop the expertise needed to successfully complete this project and
will provide him with the mentorship and support necessary to become a fully independent scientific investigator.
In line with the strategic goals of the NHLBI, the aims of this proposal focus on: (1) elucidating our understanding
of the pathobiology of EndMT and cardiovascular calcification, and (2) developing innovative new platforms to
accelerate our ability to identify therapeutic targets for these processes, thereby advancing translational
research.

## Key facts

- **NIH application ID:** 9953713
- **Project number:** 1K08HL151961-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jeffrey John Hsu
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $118,449
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953713

## Citation

> US National Institutes of Health, RePORTER application 9953713, Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Calcification (1K08HL151961-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9953713. Licensed CC0.

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