Percutaneous transluminal coronary angioplasty (PTCA) has become an attractive alternative for treating coronary artery disease (CAD) in the elderly because it is associated with less morbidity and mortality than bypass surgery. However it is not known if restenosis following PTCA is more prevalent in the elderly. Therefore, elucidating the effect of advance age on restenosis will provide important information in advising older individuals on the long term sequelae of PTCA. In order to investigate this issue we used the rat carotid artery injury model of restenosis (i.e.,the most extensively studied model of restenosis). In contrast to studies using other model systems, we found that intimal lesion formation following balloon injury was greater in young animals at early time points, and at later time points, there were no age differences in neointimal regrowth. Hormonal factors have also been shown to play an important role in restenosis. Factors dependent on the pituitary gland are involved in VSMC proliferation and migration after arterial injury as injury-induced neointimal formation is inhibited in hypophysectomized rats. The exact mechanism(s) or factor(s) dependent on the pituitary gland is not known. I an attempt to further clarify this issue and pinpoint specific hormonal factors necessary for intimal thickening, we made rats specifically hypothyroid by dietary manipulation or surgical removal of the thyroid gland. Rats fed thyroid suppressive diets (thiouracil-containing) exhibit a markedly diminished response to neointimal formation 14 days following balloon angioplasty. A similar decrease in neointima formation following balloon injury was also observed in animals following thyroidectomy. This inhibitory effect of hypothyroidism was maintained in animals who were also made hypercholesterolemic. These observations suggest that the anti-proliferative effect of hypophysectomy on neointima formation is in part specifically mediated by a deficiency in thyroid hormone.
