Mönckeberg sclerosis: a distinct entity not related to atherosclerosis. An extensive histological, immunohistochemical and ultrastructural study on 111 femoral arteries from organ and tissue donors

Intro Mönckeberg sclerosis is an uncommon form of arterial calcification occurring in the media of large to middle-sized vessels that has been erroneously associated with atherosclerosis. It has been described in generalized metabolic disorders, including hypervitaminosis D, end/stage renal disease and diabetes; however, it has been reported exceptionally even in normal young patients with no overt metabolic disease. Aim: To establish the occurrence of Mönckeberg sclerosis in a consecutive series of 111 human femoral arteries from multiorgan donors and determine whether there is a correlation between media calcification and the most common risk factors for cardiovascular disease. M&M One-hundred-eleven femoral arteries from multiorgan donors (age: 14 to 59 yrs, mean 36,5 yrs; 70 male) were histologically examined to determine the quality of the graft before cryopreservation. Selected samples were processed for electron microscopy. Immunohistochemistry was performed using a polyclonal antibody (Osx, 1:100, Abcam, Cambridge, UK) which recognizes Osterix, a transcription factor of osteoblast differentiation. The antigen-antibody reaction was revealed using a polymer system (Novolink, New Castle, UK). The percentage of Osx-positive cells was calculated on the total number of cells on 10 HPF each sample. Statistical analyses were performed using GraphPad Prism. Results Twenty-eight arteries had calcifications as the only pathological feature. Two patterns: one involving the inner elastic lamina (95%), the other the media (5%). More frequent in women (OR=1,70); young people (20-29 years; OR=1,35) affected as well; no correlation with diabetes, tabagism, hypercholesterolemia; strong correlation with hypertension (OR=1,68). Ultrastructurally calcifying matrix vesicles close to inner elastic lamina. Osx expressed in smooth muscle and mural cells of adventitia. In calcified arteries, the percentage of Osx+ cells was higher when hypertension was present (P<0,01); in this condition Osx expression in the media greatly exceeded that seen in adventitia. Conclusion This study highlights that Mönckeberg sclerosis is not a rare disease nor is it associated with microscopic features of atherosclerosis or major risk factors for cardiovascular disease. The disease is present in a young adult population, prevails in female and is associated with hypertension. Unlike previous sporadic reports the prevalent pattern is the calcification of the inner elastic lamina; this is possibly an early, reversible stage of the classical media calcification. The degree and pattern of expression of Osterix transcription factor show that smooth muscle cells have osteoblast-like potentiality able to produce osteoid matrix.