Microcalcification and thoracic aortopathy: A window into disease severity

Fletcher, A. J. et al. (2022) Microcalcification and thoracic aortopathy: A window into disease severity. Arteriosclerosis, Thrombosis, and Vascular Biology, 42(8), pp. 1048-1059. (doi: 10.1161/atvbaha.122.317111) (PMID:35770666) (PMCID:PMC9311465)

Abstract

Background: 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. Methods: One hundred one thoracic aortic specimens were collected from 57 patients with thoracic aortopathy and 18 control subjects. Standardized histopathologic scores, immunohistochemistry, and nanoindentation (tissue elastic modulus) were compared with the extent of microcalcification on von Kossa histology and 18F-sodium fluoride autoradiography. Results: Microcalcification content was higher in thoracic aortopathy samples with mild (n=28; 6.17 [2.71–10.39]; P ≤0.00010) or moderate histopathologic degeneration (n=30; 3.74 [0.87–11.80]; P <0.042) compared with control samples (n=18; 0.79 [0.36–1.90]). Alkaline phosphatase (n=26; P =0.0019) and OPN (osteopontin; n=26; P =0.0045) staining were increased in tissue with early aortopathy. Increasingly severe histopathologic degeneration was related to reduced microcalcification (n=82; Spearman ρ, −0.51; P <0.0001)—a process closely linked with elastin loss (n=82; Spearman ρ, −0.43; P <0.0001) and lower tissue elastic modulus (n=28; Spearman ρ, 0.43; P =0.026). 18 F-sodium fluoride autoradiography demonstrated 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. 18 F-sodium fluoride positron emission tomography quantifies medial microcalcification and is a feasible noninvasive imaging modality for identifying aortic wall disruption with major translational promise.

• Item Type: Articles
• Additional Information: A.J. Fletcher (FS/19/15/34155), M.G. Macaskill (RG/16/10/32375 and PG/17/83/33370), and D.E. Newby is supported by the British Heart Foundation (CH/09/002, RG/16/10/32375, and RE/18/5/34216) and is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Biomechanical and biochemical assessment was supported by the British Heart Foundation to R. Akhtar and J. Madine, respectively (PG/16/107/32681 and FS/12/61/29877). A.A.S. Tavares is funded by the British Heart Foundation (FS/19/34/34354). A.A.S. Tavares is a recipient of a Wellcome Trust Technology Development Award (221295/Z/20/Z).
• Keywords: Cardiology and Cardiovascular Medicine
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Walker, Dr Niki and Fletcher, Dr Alexander
• Authors: Fletcher, A. J., Nash, J., Syed, M. B.J., Macaskill, M. G., Tavares, A. A.S., Walker, N., Salcudean, H., Leipsic, J. A., Lim, K. H.H., Madine, J., Wallace, W., Field, M., Newby, D. E., Bouchareb, R., Seidman, M. A., Akhtar, R., and Sellers, S. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Arteriosclerosis, Thrombosis, and Vascular Biology
• Publisher: American Heart Association
• ISSN: 1079-5642
• ISSN (Online): 1524-4636
• Published Online: 30 June 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Arteriosclerosis, Thrombosis, and Vascular Biology 42(8): 1048-1059
• Publisher Policy: Reproduced under a Creative Commons licence