914-73 Effects of Hypothyroidism on Neointima Formation Following Vascular Injury in the Rat Carotid Artery

Neointima formation following vascular injury is reduced in hypophysectomized rats indicating that pituitary-derived hormonal factors likely regulate vascular smooth muscle cell (VSMC) migration and proliferation in vivo. In order to specifically investigate the role of thyroid hormone in intimal thickening following balloon injury, we made rats hypothyroid by dietary manipulation or surgical removal of the thyroid gland. Following 2 months on a thyroid suppressive diet, the extent of neointimal regrowth was compared 14 days after balloon injury in hypothyroid rats (Group 1, n=8, thyroid stimulating hormone (TSH)=9.6 micro IU/ml) and animals maintained on a normal diet (Group 2, n=8). Neointima formation was significantly attenuated in Group 1: intima/medial ratios were 0.904±0.118mm2and 1.361±0.061mm2in Groups 1 and 2 respectively, (p<0.02). Additional experiments in rats following thyroidectomy (n=3) revealed a similar significant decrease in neointima formation following balloon injury. This inhibitory effect of hypothyroidism was maintained in animals who were also made hypercholesterolemic (Group 3, n=8, TSH=10.2 micro IU/ml, total cholesterol=752mg/dl, low-density lipoprotein=674mg/dl): intima/medial ratios were 1.361±0.061mm2and 0.822±0.078mm2, in Groups 2 and 3 respectively, p<0.02. Prolonged (60 days) cholesterol feeding alone (Group 4, n=8) as suspected, did not result in elevated cholesterol levels, but also did not result in significant differences in intimal thickness when compared to animals in Group 2. These results suggest that thyroid hormone may be an important co-mitogen for the proliferative response of the rat carotid artery to balloon injury and may help partially explain the growth inhibitory effect of hypophysectomy