Variable expression of the estrogen receptor in normal and atherosclerotic coronary arteries of premenopausal women.

Background: The relative absence of coronary atherosclerosis in premenopausal women has been established. Estrogen is presumed to play a role in the protection of coronary arteries from atherosclerosis, and part of this protective effect appears to be mediated by amelioration of serum lipid profiles. However, all of the atheroprotective effect of estrogen is not explained by alteration of serum lipids.

Use of the rabbit ear artery to serially assess foreign protein secretion after site-specific arterial gene transfer in vivo. Evidence that anatomic identification of successful gene transfer may underestimate the potential magnitude of transgene expression.

Background: The development of molecular strategies for the treatment of restenosis has been hindered by low efficiencies of in vivo arterial transfection. Expression of intracellular marker proteins is generally evident in < 1% of vascular smooth muscle cells after in vivo arterial transfection. Efforts to improve the efficiency of in vivo gene transfer have been further impeded by the use of transgenes encoding for intracellular marker proteins, necessitating tissue removal and limiting survey for expression to one point in time.

Liposome-mediated gene transfer into human vascular smooth muscle cells.

Background: Complexing recombinant DNA with cationic liposomes is a convenient means of introducing foreign genes into cells (lipofection) and could potentially form the basis for genetically modifying diseased blood vessels in patients. The mechanism of lipofection is incompletely understood, but it is recognized that the degree of successful gene transfer is highly dependent on cell type. To date, there has been no reported experience with lipofection of human vascular smooth muscle cells.

Proliferative activity in peripheral and coronary atherosclerotic plaque among patients undergoing percutaneous revascularization.

We evaluated the proliferative activity of human atherosclerotic lesions associated with active symptoms of ischemia, by assessing the expression of the proliferating cell nuclear antigen (PCNA). We confirmed in vitro that PCNA, an essential component of the DNA synthesis machinery, is selectively expressed in proliferating human vascular smooth muscle cells. 37 atherosclerotic lesions (18 primary and 19 restenotic) retrieved by directional atherectomy from either coronary or peripheral arteries were then studied for the expression of PCNA, using in situ hybridization or immunohistochemistry.

Prevention of smooth muscle cell outgrowth from human atherosclerotic plaque by a recombinant cytotoxin specific for the epidermal growth factor receptor.

Smooth muscle cell proliferation in the intima of arteries is a principal event associated with vascular narrowing after balloon angioplasty and bypass surgery. Techniques for limiting smooth muscle cell proliferation, however, have not as yet yielded any therapeutic benefit for these conditions. This may reflect the present lack of sufficiently potent and specific inhibitors of smooth muscle cell proliferation.