Microcalcification and thoracic aortopathy: a window into disease severity

Alexander J Fletcher*, Jennifer Nash, Maaz Syed, Mark Macaskill, Adriana A S Tavares, Niki Walker, Hannah Salcudean, Jonathon A. Leipsic, Kelvin Lim, Jillian Madine, William Wallace, Mark Field, David E Newby, Rihab Bouchareb, Michael Seidman, Riaz Akhtar, Stephanie Sellers

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective
Patients with thoracic aortopathy are at increased risk of catastrophic aortic dissection, carrying with it substantial mortality and morbidity. Although granular medial calcinosis (medial microcalcification) has been associated with thoracic aortopathy, its relationship to disease severity has yet to be established.

Approach and Results
One hundred and one thoracic aortic specimens were collected from 57 patients with thoracic aortopathy and 18 control subjects. Standardized histopathological scores, immunohistochemistry and nanoindentation (tissue elastic modulus) were compared to the extent of microcalcification on von Kossa histology and 18F-sodium fluoride autoradiography.

Microcalcification content was higher in thoracic aortopathy samples with mild (n=28; 6.17 [2.71 to 10.39], p≤0.00010) or moderate histopathological degeneration (n=30; 3.74 [0.87, to 11.80], p<0.042) compared with control samples (n=18, 0.79 [0.36 to 1.90]). Alkaline phosphatase (n=26, p=0.0019) and osteopontin (n=26, p=0.0045) staining were increased in tissue with early aortopathy. Increasingly severe histopathological degeneration was related to reduced microcalcification (n=82, Spearman’s rho -0.51, p<0.0001), a process closely linked with elastin loss (n=82; Spearman’s rho = -0.43, p<0.0001) and lower tissue elastic modulus (n=28; Spearman’s rho = 0.43, p=0.026). 18F-Sodium fluoride autoradiography demonstrated very good correlation with histologically quantified microcalcification (n=66; r=0.76, p<0.001), and identified areas of focal weakness in vivo.

Conclusions
Medial microcalcification is a marker of aortopathy, although progression to severe aortopathy is associated with loss of both elastin fibers and microcalcification. 18F-Sodium fluoride positron emission tomography quantifies medial microcalcification and is a feasible non-invasive imaging modality for identifying aortic wall disruption with major translational promise.

Original languageEnglish
JournalArteriosclerosis, Thrombosis, and Vascular Biology
DOIs
Publication statusPublished - 30 Jun 2022

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