Permalink : http://hdl.handle.net/2115/53319

KEYWORDS : klotho;medial calcification;vascular smooth muscle cell;matrix vesicles;trans-differentiation

Klotho deficient （kl/kl） mice are well known to　develop hyperphosphatemia and resultant Möncheberg’s vascular sclerosis, which consists of elongated or　fragmented elastic lamellae and abundant collagen fibrils inside the vessels. Instead of normal vascular smooth muscle cells （VSMCs）, the tunica media of the kl/kl aorta has cells rich with abundant endoplasmic reticulum and Golgi apparatus, somewhat resembling osteoblasts. There were many matrix vesicle-like structures and calcifying nodules in the vicinity of these osteoblast-like cells in kl/kl aorta. The calcifying nodules seem to trigger calcification in the elastic lamellae, without promoting it in the collagen fibrils inside the kl/kl aorta. Also, mineral deposition was observed within the intravascular amorphous organic component, suggesting dystrophic calcification. Thus, two possible pathways for vascular calcification exist: one mediated by matrix vesicle-like structures, and another taking place after the deposition of calcium phosphates in the amorphous organic component. Compared to the latter, which consists of the classical view of intravascular calcification, the former appears to mimic osteoblastic mineralization in bone, and could be the result of trans-differentiation of VSMCs into osteoblastic cells. In this work, we will review our current findings on the process of medial vascular calcification found in kl/kl mice.