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.
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
VALENTE, SABRINA;PACILLI, ANNALISA;PINI, RODOLFO;PASQUINELLI, GIANANDREA;STELLA, ANDREA
2013
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
