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

J Nucl Cardiol. 2021 Oct;28(5):2207-2214. doi: 10.1007/s12350-019-02004-3. Epub 2020 Jan 2.

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.

Keywords: 18F-NaF PET/CT imaging; PTH; Treadmill exercise; aortic; calcification; hyperlipidemia; microarchitecture.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcification, Physiologic / physiology*
  • Disease Models, Animal
  • Fluorodeoxyglucose F18 / administration & dosage
  • Fluorodeoxyglucose F18 / therapeutic use
  • Hyperlipidemias / complications*
  • Hyperlipidemias / diagnostic imaging
  • Mice
  • Physical Conditioning, Animal / methods
  • Physical Conditioning, Animal / standards*
  • Physical Conditioning, Animal / statistics & numerical data
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Plaque, Atherosclerotic / physiopathology
  • Positron Emission Tomography Computed Tomography / methods
  • Positron Emission Tomography Computed Tomography / statistics & numerical data
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / therapeutic use

Substances

  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18