Estrogen receptor transcription and transactivation: Basic aspects of estrogen action

Estrogen signaling has turned out to be much more complex and exciting than previously thought; the paradigm shift in our understanding of estrogen action came in 1996, when the presence of a new estrogen receptor (ER), ERβ, was reported. An intricate interplay between the classical ERα and the novel ERβ is of paramount importance for the final biological effect of estrogen in different target cells

The molecular biology of vein graft atherosclerosis and myointimal hyperplasia

Vein graft atherosclerosis and myointimal hyperplasia can result in critical stenosis and subsequent graft failure. Injury to the vein wall and the healing response to this injury appear to underlie the formation of these graft lesions. Although the exact nature of the injury remains controversial, loss of endothelial integrity with exposure of the subendothelial intima are believed to stimulate cellular adhesion with smooth muscle migration, proliferation, and phenotypic transformation. Recent progress has been made in understanding the molecular and cellular events involved in this process. The roles of endothelial cells, smooth muscle cells, macrophages, and T lymphocytes continue to be defined as does the role of peptide growth factors such as platelet-derived growth factor, fibroblast growth factor, transforming growth factor, and insulin-like growth factor. Additional regulation by cytokines, adhesion molecules, proteoglycans of the extracellular matrix, and hemodynamic flow patterns helps determine the response of the vein wall to injury. A thorough understanding of this multifactorial process will permit molecular techniques to genetically modify vascular cells in order to deliver appropriate peptides or pharmacologic agents, thereby improving the function of vein bypass grafts

Inhibition of myointimal proliferation of the rat carotid artery by the peptides, angiopeptin and BIM 23034.

Proliferation of vascular smooth muscle is an early and major event in the formation of an atherosclerotic lesion. Here we report for the first time the inhibitory effects on myointimal proliferation of the rat carotid artery by a synthetic peptide, angiopeptin, and its closely related congener, BIM 23034. Proliferation was initiated in the carotid artery of anesthetized rats by air-drying of the endothelium. After 15 days the rats were killed and the carotid artery was pressure-fixed and subjected to morphologic analysis for evaluation of the degree of myointimal thickening. Five synthetic somatostatin-like peptides were tested by pretreating rats (20 and 50 micrograms/kg/rat s.c. daily) for 2 days prior to and for 5 days after the endothelial injury. Angiopeptin and the closely related octapeptide (BIM 23034) significantly inhibited myointimal thickening. Angiopeptin was also effective when the pretreatment period was reduced from 2 days to 30 min. The inhibitory effect of angiopeptin was further confirmed in an additional experiment involving [3H]thymidine incorporation. In this experiment angiopeptin (100 micrograms/kg/day s.c.) was also administered for 2 days prior to and five days following the endothelial injury and it significantly inhibited thymidine uptake. All the peptides tested inhibit the release of growth hormone. However, only angiopeptin and BIM 23034 inhibited myointimal proliferation. Thus the effect of angiopeptin and its congener is unlikely to be mediated through growth hormone. Since angiopeptin inhibits myointimal proliferation it may have clinical utility in preventing restenosis following angioplasty and coronary artery by-pass procedures