# Role of intermittent activation of parathyroid hormone receptor in exercise-induced vascular calcification

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $552,886

## Abstract

PROJECT SUMMARY/ABSTRACT
Vascular calcification, especially coronary artery calcification (CAC), is associated with increased risk of
cardiovascular disease, whereas regular physical activity is associated with decreased risk. Thus, one would
predict that physically active individuals would have less CAC, yet clinical studies show the opposite. Elite
athletes actually have more CAC than their sedentary counterparts even though they have lower cardiac event
rates. The objective of this proposal is to determine the mechanism of this paradox. As clinical studies show
that coronary plaques containing large, contiguous calcium deposits are associated with less cardiovascular
risk than fragmented calcium deposits, one possibility would be that exercise remodels calcium deposits into a
more stable microarchitecture. Theoretical analytical modeling also predicts that decreased surface area of
calcium deposits is expected to reduce plaque rupture risk. Interestingly, a single bout of exercise in humans
and mice causes a transient 1.8-fold elevation of parathyroid hormone (PTH), and intermittent treatment of
PTH in humans and mice causes increased bone growth, which shares signaling mechanisms with vascular
calcification. Our recent findings provide an association between PTH and microarchitecture of vascular
calcium deposits, where intermittent PTH treatment reduces the surface area of aortic calcium deposits in
hyperlipidemic mice with pre-existing vascular calcification. Our preliminary studies provide a more direct
association of exercise with the remodeling of vascular calcium deposits. We found that hyperlipidemic mice
with pre-existing aortic calcification on a 9-week treadmill regimen had increased serum PTH levels, increased
PTH receptor levels in the aortic roots, and decreased mineral surface area by nuclear imaging and
histomorphometry. Thus, we hypothesize that exercise, through activation of the vascular PTH1 receptor,
shifts the microarchitecture of calcium deposits toward a more stabilized form, reducing the rupture risk. We
will test our hypothesis using 3 Specific Aims to determine: 1) whether loss of PTH1 receptor activation
blocks the exercise-induced remodeling of vascular calcium deposits; 2) the relative contributions of circulating
PTH and local (tissue) PTH related peptide (PTHrP) on the exercise-induced changes in microarchitecture;
and 3) effects of confounding factors (sex, exercise dose, diet, and species) on exercise-induced changes in
the SMC transcriptome and vascular calcium deposit microarchitecture. We will use pharmacologic, genetic,
and surgical models, and the endpoints will include progression and microarchitecture of aortic calcium
deposits, including size and surface area based on structural analyses (serial 18F-µPET/µCT,
histomorphometry), transcriptome analysis, and functional biomechanical analyses using a balloon catheter as
a mechanical sensor for rupture vulnerability. The proposed research is significant beca...

## Key facts

- **NIH application ID:** 10320968
- **Project number:** 5R01HL151391-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Linda L. Demer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $552,886
- **Award type:** 5
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320968

## Citation

> US National Institutes of Health, RePORTER application 10320968, Role of intermittent activation of parathyroid hormone receptor in exercise-induced vascular calcification (5R01HL151391-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10320968. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*