Thyrotropin induces atherosclerosis by upregulating large conductance Ca²⁺-activated K⁺ channel subunits

Hypothyroidism is associated with elevated levels of serum thyrotropin (TSH), which have been shown to promote abnormal proliferation of vascular smooth muscle cells and contribute to the development of atherosclerosis. However, the specific mechanisms underlying the TSH-induced abnormal proliferation of vascular smooth muscle cells remain unclear. The objective of this study was to investigate the role of TSH in the progression of atherosclerosis. Our research findings revealed that hypothyroidism can trigger early atherosclerotic changes in the aorta of Wistar rats. In alignment with our in vitro experiments, we observed that TSH induces abnormal proliferation of aortic smooth muscle cells by modulating the expression of α and β1 subunits of large conductance Ca²⁺-activated K⁺ (BK_Ca) channels within these cells via the cAMP/PKA signaling pathway. These results collectively indicate that TSH acts through the cAMP/PKA signaling pathway to upregulate the expression of α and β1 subunits of BK_Ca channels, thereby promoting abnormal proliferation of arterial smooth muscle cells. These findings may provide a basis for the clinical prevention and treatment of atherosclerosis caused by elevated TSH levels.