Atorvastatin Promotes Macrocalcification, But Not Microcalcification in Atherosclerotic Rabbits: An 18F-NaF PET/CT Study

J Cardiovasc Pharmacol. 2021 Oct 1;78(4):544-550. doi: 10.1097/FJC.0000000000001088.

Abstract

Introduction: Our study aimed to investigate the effect of atorvastatin on plaque calcification by matching the results obtained by 18F-sodium fluoride (18F-NaF) positron emission tomography (PET)/computed tomography (CT) with data from histologic sections.

Methods and results: The rabbits were divided into 2 groups as follows: an atherosclerosis group (n = 10) and an atorvastatin group (n = 10). All rabbits underwent an abdominal aortic operation and were fed a high-fat diet to induce atherosclerosis. Plasma samples were used to analyze serum inflammation markers and blood lipid levels. 18F-NaF PET/CT scans were performed twice. The plaque area, macrophage number and calcification were measured, and the data from the pathological sections were matched with the 18F-NaF PET/CT scan results. The mean standardized uptake value (0.725 ± 0.126 vs. 0.603 ± 0.071, P < 0.001) and maximum standardized uptake value (1.024 ± 0.116 vs. 0.854 ± 0.091, P < 0.001) significantly increased in the atherosclerosis group, but only slightly increased in the atorvastatin group (0.616 ± 0.103 vs. 0.613 ± 0.094, P = 0.384; 0.853 ± 0.099 vs.0.837 ± 0.089, P < 0.001, respectively). The total calcium density was significantly increased in rabbits treated with atorvastatin compared with rabbits not treated with atorvastatin (1.64 ± 0.90 vs. 0.49 ± 0.35, P < 0.001), but the microcalcification level was significantly lower. There were more microcalcification deposits in the areas with increased radioactive uptake of 18F-NaF.

Conclusions: Our study suggests that the anti-inflammatory activity of atorvastatin may promote macrocalcification but not microcalcification within atherosclerotic plaques. 18F-NaF PET/CT can detect plaque microcalcifications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Abdominal / diagnostic imaging
  • Aorta, Abdominal / drug effects*
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / pathology
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atorvastatin / toxicity*
  • Calcium / metabolism
  • Disease Models, Animal
  • Fluorine Radioisotopes*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / toxicity*
  • Male
  • Plaque, Atherosclerotic
  • Positron Emission Tomography Computed Tomography*
  • Rabbits
  • Radiopharmaceuticals*
  • Sodium Fluoride*
  • Vascular Calcification / chemically induced*
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / metabolism
  • Vascular Calcification / pathology

Substances

  • Fluorine Radioisotopes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Radiopharmaceuticals
  • Sodium Fluoride
  • Atorvastatin
  • Fluorine-18
  • Calcium