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Changes in microarchitecture of atherosclerotic calcification assessed by 18F-NaF PET and CT after a progressive exercise regimen in hyperlipidemic mice

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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Despite the association of physical activity with improved cardiovascular outcomes and the association of high coronary artery calcification (CAC) scores with poor prognosis, elite endurance athletes have increased CAC. Yet, they nevertheless have better cardiovascular survival. We hypothesized that exercise may transform vascular calcium deposits to a more stable morphology.

Methods

To test this, hyperlipidemic mice (Apoe−/−) with baseline aortic calcification were separated into 2 groups (n = 9/group) with control mice allowed to move ad-lib while the exercise group underwent a progressive treadmill regimen for 9 weeks. All mice underwent blood collections and in vivo 18F-NaF μPET/μCT imaging both at the start and end of the exercise regimen. At euthanasia, aortic root specimens were obtained for histomorphometry.

Results

Results showed that, while aortic calcification progressed similarly in both groups based on µCT, the fold change in 18F-NaF density was significantly less in the exercise group. Histomorphometric analysis of the aortic root calcium deposits showed that the exercised mice had a lower mineral surface area index than the control group. The exercise regimen also raised serum PTH levels twofold.

Conclusion

These findings suggest that weeks-long progressive exercise alters the microarchitecture of atherosclerotic calcium deposits by reducing mineral surface growth, potentially favoring plaque stability.

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Abbreviations

CAC:

Coronary artery calcification

PET:

Positron emission tomography

CT:

Computed tomography

Apoe:

Apolipoprotein E

NaF:

Sodium fluoride

ROI:

Region of interest

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Acknowledgments

We would like to acknowledge Drs. Jason Lee, Arion Chatziioannou, and Sotirios Tetradis for support with imaging, as well as the use of the Mouse Physiology Laboratory of the Department of Physiology and the Pre-Clinical Facility of the Crump Institute for Molecular Imaging at the California NanoSystems Institute.

Disclosure

The authors declare that they have no competing interests or conflict of interests.

Author information

Author notes

  1. Jeffrey J. Hsu and Felicia Fong have contributed equally.

Authors and Affiliations

  1. Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

    Jeffrey J. Hsu MD, PhD, Felicia Fong, Radha Patel, Rong Qiao BS, Karen Lo BS, Victoria Le BS, Chi-Hong Tseng PhD, Linda L. Demer MD, PhD & Yin Tintut PhD

  2. School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA

    Akrivoula Soundia DDS

  3. Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA

    Chih-Chiang Chang MS & Linda L. Demer MD, PhD

  4. Department of Physiology, University of California, Los Angeles, Los Angeles, CA, USA

    Linda L. Demer MD, PhD & Yin Tintut PhD

  5. Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA, USA

    Yin Tintut PhD

  6. Center for the Health Sciences A2-237, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA, 90095-1679, USA

    Yin Tintut PhD

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  1. Jeffrey J. Hsu MD, PhD
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Correspondence to Yin Tintut PhD.

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Funding

This work was supported by the National Institutes of Health (HL12109, HL137647, AG61586, P30AG028748), and an American Heart Association Post-Doctoral Research Fellowship (18POST34030272). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Hsu, J.J., Fong, F., Patel, R. et al. Changes in microarchitecture of atherosclerotic calcification assessed by 18F-NaF PET and CT after a progressive exercise regimen in hyperlipidemic mice. J. Nucl. Cardiol. 28, 2207–2214 (2021). https://doi.org/10.1007/s12350-019-02004-3

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