| Vascular smooth muscle cells (SMCs), the major cellular constituent of the artery, synthesize the bulk of fibrillar collagen in the vessel wall. The transcription factor B-myb has been characterized as a negative regulator of collagen gene expression by vascular SMCs in culture. To analyze B-myb function in vivo, a mouse model was generated with human B-myb cDNA driven by the basal cytomegalovirus promoter. In three transgenic lines, human B-myb was expressed in all tissues tested. Importantly, B-Myb protein expression was elevated in the aorta. A dramatic decrease in elastin mRNA levels and a moderate decrease in α1(I) collagen mRNA was observed, and this was confirmed in vascular SMCs isolated from the transgenic mice. These results suggest that expression of B-myb in vivo leads to a repression of matrix gene expression in aortic SMCs in vivo. Moreover, elastin is identified as a new target of B-Myb. Thus, overexpression of B-myb may have the potential to inhibit cardiovascular fibrosis.; Excessive proliferation of SMCs and subsequent matrix deposition are the hallmarks of atherosclerosis and restenosis. Green tea contains polyphenols (GTPs), which inhibit development of atherosclerotic lesions. The most prevalent GTP, epigallochatechin-3-gallate (EGCG), is known for its anti-proliferative effects. The effects of GTPs on aortic SMC proliferation were examined. Cell count and TUNEL assays showed that treatment with a GTP mixture or purified EGCG at doses of 40–50 μg/ml slowed SMC proliferation, while a higher dose of 80 μg/ml EGCG also induced cell death. Apoptosis occurred mainly in proliferating, subconfluent cultures, and was minimal at higher confluency. Treatment with EGCG induced expression of p53 and its target, the cyclin dependent kinase inhibitor p21. Inhibition of p53 reduced EGCG-mediated apoptosis. The increase in p53 protein in SMCs was due to increased p53 protein stability. In some cell types, NF-κB has been shown to be required for p53 mediated cell death. EGCG induced functional NF-κB (p50/p65) complexes, and inhibition of this activity reduced the extent of cell death. Thus, EGCG arrests proliferation and induces cell death in p53- and NF-κB-dependent fashion. These results provide a mechanism by which GTPs prevent the development of atherosclerosis. |
