Arterial calcification in mice after freeze-thaw injury.
Vascular calcification is highly correlated with atherosclerosis and cardiovascular disease and is a significant predictor of cardiovascular morbidity and mortality. Studies in mice indicate a genetic contribution to this dystrophic extra osseous calcification. We sought to elaborate a method to induce dystrophic arterial calcification in mice and further examine the pathogenetical mechanisms involved in the phenotype. We established a method of freeze-thaw injury of the infrarenal aorta producing a limited tissue necrosis and histologically investigated the occurrence of dystrophic calcification within the aortic wall 1, 3 and 7 days after injury in C57BL/6 (a mouse strain shown to be resistant to dystrophic cardiac calcification after injury) and C3H/He (susceptible to dystrophic cardiac calcification). C57BL/6 mice exhibited no dystrophic calcification at all within the vessel wall upon injury of the infrarenal aorta (0/5 mice 1 day after injury and 0/10 animals 7 days after injury). By contrast C3H/He mice displayed a remarkable extent of calcification mainly present within the media of the infrarenal aorta which was evident as early as 24 h (three out of five animals 1 day after injury) and reached its maximum extent 7 days after injury (10 out of 10 animals at the seventh postoperative day, p<0.001 compared to C57BL/6 mice). Upon immuno-histological analysis calcification was accompanied by the occurrence of certain bone-matrix associated proteins. Osteopontin and Bone Morphogenetic Protein 2/4 expression was detected co-localized with the calcified lesions. Our results demonstrate that freeze-thaw injury of the infrarenal aorta is a sufficient method to induce dystrophic arterial calcification in mice. We present evidence that the occurrence of arterial calcification in C3H/He mice seems to be actively regulated by certain bone-matrix associated proteins.
Doehring
Lars C
LC
Medizinische Klinik II, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. lars.doehring@uk-sh.de
Kaczmarek
Piotr M
PM
Ehlers
EvaM
E
Mayer
Björn
B
Erdmann
Jeanette
J
Schunkert
Heribert
H
Aherrahrou
Zouhair
Z
D000818:Animals; D001011:Aorta / Q000473:pathology; D001157:Arterial Occlusive Diseases / Q000209:etiology* / Q000473:pathology; D002114:Calcinosis / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005615:Freezing; D007053:Ice / Q000009:adverse effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D007053:Ice