# Role of ABCC6 in cardivascular calcification

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $516,873

## Abstract

Abstract
Pseudoxanthoma elasticum (PXE) is genetic disorder characterized by degeneration of elastic fibers that leads
to dermatologic, ocular and cardiovascular abnormalities, involving progressive calcification of the soft tissues.
Calcification can occur within the heart muscle, particularly after injury, and predisposes these patients to
cardiac dysfunction or sudden death from ventricular arrhythmias. PXE is caused by mutations in the ATP
Binding Cassette C6 transporter gene (ABCC6) yet little is understood how deficiency of ABCC6 induces
ectopic calcification in multiple soft tissues. Calcification of soft tissues is thought to be an active process
where bone forming osteoblast-like cells are recruited to the affected tissue and cause mineralization of the
extracellular matrix, a process analogous to cancellous bone formation. However the nature of the cells
contributing to soft tissue calcification in the heart and other organs in PXE and how this is regulated by
ABCC6 are unknown. The Deb lab has recently shown that cardiac fibroblasts are not terminally differentiated
and presents preliminary data to suggest that fibroblast adopt osteogenic fates and directly contribute to heart
muscle calcification in a mouse model of PXE. The Lusis lab was one of the first labs to identify and clone
ABCC6 as an important gene regulating soft tissue calcification. In this multi PI proposal, the Deb and Lusis
labs interrogate the role of fibroblast plasticity in directly contributing to heart muscle calcification in ABCC6
deficient animals, investigate i) spatio-temporal dynamics of fibroblast-osteoblast transitions ii) biochemical
mechanisms regulating fibroblast mediated calcification and –iii) the physiologic significance of fibroblast
mediated calcification. We provide preliminary data that mechanisms regulating calcification in ABCC6
deficiency are dysregulated in other common causes of ectopic calcification such as human heart valve
calcification and investigate strategies to inhibit final common pathways mediating ectopic calcification,
regardless of the underlying pathology.

## Key facts

- **NIH application ID:** 9852336
- **Project number:** 5R01HL137241-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Arjun Deb
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $516,873
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852336

## Citation

> US National Institutes of Health, RePORTER application 9852336, Role of ABCC6 in cardivascular calcification (5R01HL137241-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852336. Licensed CC0.

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