Aortic intimal thickening and myosin isoform expression in hyperthyroid rabbits.

Abstract

The potential effect of thyroid hormones on the expression of cytoskeletal and cytocontractile proteins of vascular smooth muscle cells (SMCs) was examined by a panel of monoclonal antibodies and immunocytochemical procedures. L-Thyroxine was administered to adult New Zealand White rabbits for as long as 26 days, and the aortic SMC composition was studied at days 1, 2, 7, 15, and 26 from the beginning of hormonal treatment. A diffuse intimal thickening of the aorta became visible after 7 days of thyroxine administration. Histological and histochemical examination of intimal tissues from hyperthyroid rabbits revealed the presence of a homogeneous Sudan black-negative cell population. In immunofluorescence tests the intimal cells were found to be negative for antibodies specific for monocyte/macrophage or desmin and homogenously reactive (positive) for antibodies to vimentin and smooth muscle (SM) alpha-actin, thus indicating that cells present in the thickened intima were of the SM type. In addition, intimal SMCs from aortas of hyperthyroid rabbits showed a myosin isoform content similar to that found in normal developing aortic SM and in a specific medial SMC subpopulation of aortas from adult euthyroid animals. In the media underlying the intimal thickening, almost all the SMCs switched their myosin isoform expression toward the "immature" phenotype after 2 days of thyroxine treatment. When the level of thyroid hormones was reduced by propylthiouracil treatment, the medial SMC subpopulation with the immature myosin isoform content present in euthyroid rabbits completely disappeared. The study of DNA synthesis-related bromodeoxyuridine incorporation in aortas from hyperthyroid rabbits showed the presence of labeled nuclei in medial SMCs before the appearance of the intimal thickening as well as in the thickened intima and in the underlying media at days 7 and 15. These results are consistent with a specific role for thyroid hormones in inducing proliferation/migration of medial SMCs into the intima. Moreover, the switch in the expression of myosin isoforms induced by thyroid hormones appears to precede the accumulation of medial SMCs in the intima.