Cartilaginous metaplasia and calcification in aortic allograft is associated with transforming growth factor beta 1 expression.
BACKGROUND
Calcification of homografts and vascular conduits is poorly understood. Mechanisms leading to calcification were studied in a rat model of aortic allografts.


METHODS
Rat aortas from Lew1W (RT1(u)) were transplanted into Lew1A (RT1(a)). Animals were killed at 30 days and 180 days, and aortic grafts were removed and analyzed for histologic and immunohistologic studies.


RESULTS
Intimal surface increased progressively over 6 months and was the site of important modifications. Intimal cellular population changed from a leukocyte (CD45, OX1-OX30)- and macrophage (CD68, ED-1)-based population at 30 days to predominantly alpha-smooth muscle actin-expressing cells at 180 days. At 180 days, allografts were characterized by an abundant extracellular matrix composed of collagen and elastic fibers associated with extensive calcification (von Kossa staining) located in the intima and media. Osteoblastic activity was present in calcified lesion as shown by alkaline phosphatase activity. At 180 days, numerous chondrocytes (protein S100-positive and alpha-smooth muscle actin-negative) were present focally in the media. However, double immunostaining revealed that a cellular population within the media with a chondrocyte-like morphology was alpha-smooth muscle actin-positive and S100-negative. Active form of transforming growth factor beta1 was expressed from 30 to 80 days in the medial and intimal layers.


CONCLUSIONS
These observations suggest that alpha-smooth muscle actin-positive cells within aortic allografts are eventually transformed to a chondrocyte-like structure, leading to vascular cartilaginous metaplasia associated with the expression of transforming growth factor beta1 and could be a potential pathway leading to extensive vascular wall calcification in allografts through endochondral ossification.
Mathieu
P
P
Quebec Heart Institute, Hôpital Laval, Sainte-Foy, Canada. prmathieu@hotmail.com
Roussel
J C
JC
Dagenais
F
F
Anegon
I
I
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology* / Q000637:transplantation*; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D002114:Calcinosis / Q000473:pathology*; D019902:Chondrocytes / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053773:Transforming Growth Factor beta1; D014184:Transplantation, Homologous
D015415:Biomarkers; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1