# Novel Molecular Regulators of Vascular Calcification

> **NIH NIH F32** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $85,558

## Abstract

PROJECT SUMMARY
Atherosclerotic disease is characterized by intimal vascular calcification, which is an
independent and potent risk factor for morbidity and mortality in coronary artery disease, stroke,
and aortic pathologies. Vascular calcification is an active cell-mediated process that involves the
phenotypic switch of vascular smooth muscle cells (VSMC) from contractile to osteogenic cells.
Understanding the molecular mechanisms driving vascular calcification is critical for developing
targeted therapies. In our lab, we have identified novel single nucleotide polymorphisms (SNPs)
in the arylsulfatase E (ARSE) locus on the X chromosome that are associated with coronary
artery calcification. Our preliminary data demonstrate that adenovirus-mediated overexpression
of ARSE in VSMCs leads to increased calcification and that conversely, reduced expression of
ARSE with siRNA prevents calcification of VSMCs. We have identified SULF1, a protein related
to ARSE in the same family of sulfatases, as having similar effects on vascular calcification as
that demonstrated in our in vitro studies for ARSE. Based on our previous studies, we have also
identified histone deacetylase 4 and 5 (HDAC4/5) to be important regulators of vascular
calcification, mediated by subcellular localization of HDAC4/5 in the cytosol through
phosphorylation by focal adhesion kinase (FAK). The goal of this project is to perform in vitro, ex
vivo, and in vivo studies to test the hypothesis that ARSE/SULF1 and HDAC4/5 are important
and novel determinants of vascular calcification that induce the phenotypic switch of VSMCs to
osteogenic cells. Overall, my aim is to unravel novel molecular mechanisms underlying VSMC
function and calcification that contribute to the pathogenesis of atherosclerotic cardiovascular
disease. Through world-class didactic opportunities and close mentorship from experts in the
field of vascular biology and genomics, I will complete this project having gained valuable skills
in bioinformatics, in vitro cellular assays modeling vascular disease, in vivo mouse model
experiments, scientific communication and laboratory leadership. By the end of the fellowship, I
will have gained skills necessary to develop my own research program and ultimately launch my
own career as an NIH-funded vascular surgeon scientist.

## Key facts

- **NIH application ID:** 10894597
- **Project number:** 5F32HL164025-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Sujin Lee
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $85,558
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894597

## Citation

> US National Institutes of Health, RePORTER application 10894597, Novel Molecular Regulators of Vascular Calcification (5F32HL164025-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894597. Licensed CC0.

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