Estrogen receptor expression and synthesis in the human internal thoracic artery

The inhibition of vascular smooth muscle cell proliferation is mediated through two intracellular estrogen receptors (ERs), ER-alpha and ER-beta. Deletion variants of ER-alpha have been decribed for cultures of smooth muscle cells. The internal thoracic artery is frequently used as coronary artery bypass graft, yet neither has it been studied for the expression of ER subtypes nor for the synthesis of the ERs in morphologically hetergeneous smooth muscle cells. Using nested RT-PCR, we have demonstrated the mRNA for ER-alpha splicing variants in intact human internal thoracic arteries. The 7A deletion variant occurred in 8 out of 12 cases, the full-length transcript in three cases. The full-length transcript was always found for the ER-beta. Immunolocalization revealed ER-positive nuclei in the desmin-positive subset of smooth muscle cells, but not in cytokeratin (CK)-positive cells of the thickened intima. Morphological evidence is presented suggesting that ER synthesis is high in the tunica media when cell proliferation of smooth muscle cells is increased. We conclude that, in internal thoracic arteries, the 7A deletion variant of ER-a occurs in 75%, whereas the full-length transcript is found in all cases. The significance remains unclear.