OVEREXPRESSION OF TRANSFORMING-GROWTH-FACTOR BETA-1 IN ARTERIAL ENDOTHELIUM CAUSES HYPERPLASIA, APOPTOSIS, AND CARTILAGINOUS METAPLASIA

Uninjured rat arteries transduced with an adenoviral vector expressing an active form of transforming growth factor beta 1 (TGF-beta 1) deve loped a cellular and matrix-rich neointima, with cartilaginous metapla sia of the vascular media. Explant cultures of transduced arteries sho wed that secretion of active TGF-beta 1 ceased by 4 weeks, the time of maximal intimal thickening. Between 4 and 8 weeks, the cartilaginous metaplasia resolved and the intimal lesions regressed almost completel y, in large part because of massive apoptosis, Thus, locally expressed TGF-beta 1 promotes intimal growth and appears to cause transdifferen tiation of vascular smooth muscle cells into chondrocytes. Moreover, T GF-beta 1 withdrawal is associated with regression of vascular lesions . These data suggest an unexpected plasticity of the adult vascular sm ooth muscle cell phenotype and provide an etiology for cartilaginous m etaplasia of the arterial wall, Our observations may help to reconcile divergent views of the role of TGF-beta 1 in vascular disease.