title: Breast arterial calcification in chronic kidney disease: absence of smooth muscle apoptosis and osteogenic transdifferentiation.
abstract: The pathophysiology of medial arterial calcification in chronic kidney disease (CKD) is unclear but has been ascribed to phenotypic changes in vascular smooth muscle, possibly in conjunction with intimal proliferation and atherosclerosis. As the prevalence of calcification in breast arteries is increased in women with CKD and end-stage renal disease (ESRD), this was examined histologically in mastectomy specimens from 19 women with CKD or ESRD. Arterial calcification was present in 18, was exclusively medial, and occurred in vessels as small as arterioles. Intimal thickening was common but unrelated to calcification. There was no evidence of atherosclerosis. The earliest calcification presented as small punctate lesions scattered throughout the media, often with calcification of the internal elastic lamina. Arterial calcification was present in all samples from an age- and diabetes-matched cohort without CKD but was much milder. While smooth muscle cell density was reduced one-third in arteries from patients with ESRD, the cells appeared normal, expressed SM22α, and exhibited no apoptosis. Staining for the bone-specific protein osteocalcin, the osteoblastic transcription factors Runx2 or osterix, or the chondrocytic transcription factor SOX9 was absent in regions of early calcification. Thus, medial calcification in breast arteries of patients with CKD can occur in the absence of smooth muscle cell apoptosis and/or osteogenic transdifferentiation. This suggests that the pathologic mineralization process may differ from one arterial type to the other.
authors.affiliation: Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: W Charles
authors.initials: WC
authors.lastname: O'Neill
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Adams
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001158:Arteries / Q000473:pathology; D001940:Breast / Q000098:blood supply* / Q000473:pathology; D054338:Cell Transdifferentiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D010012:Osteogenesis; D051436:Renal Insufficiency, Chronic / Q000473:pathology*; D061205:Vascular Calcification / Q000473:pathology*