Microsatellite mutation of type II transforming growth factor-beta receptor is rare in atherosclerotic plaques

A somatic mutation within a microsatellite polyA tract in the coding region of the type II transforming growth factor (TGF)-beta receptor gene was rep orted to occur in human atherosclerotic and restenotic lesions. This mutati on occurs frequently in colorectal cancer with the replication error repair phenotype and results in loss of sensitivity to the growth inhibitory effe cts of TGF-beta in cells from the tumors. The mutation was proposed to acco unt for the clonal expansion of vascular smooth muscle cells observed in at herosclerotic plaques, through loss of the growth inhibitory effect of TGF- beta. The frequency of the mutation and the extent of clonal expansion of t he mutated cells have major implications for the mechanism of atherogenesis and therapeutic strategies. We analyzed a set of 22 coronary arterial and 9 aortic samples containing early to advanced atherosclerotic lesions fbr t he mutation in the type II TGF-beta receptor polyA tract. Only 1 coronary a rterial sample from an advanced lesion showed detectable amounts of the mut ation, present at a low level (8% of the DNA sample). The data imply that t he mutation occurs only at low frequency and is not a major mechanistic con tributor to the development of atherosclerosis.