Thyroid stimulating hormone exhibits the impact on LDLR/LDL-c via up-regulating hepatic PCSK9 expression

Abstract Context Thyroid stimulating hormone (TSH) has received increasing attention as being closely associated with increased low-density lipoprotein cholesterol (LDL-c) level and higher atherosclerotic risks. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is known for increasing circulating LDL-c level by inducing LDL receptor degradation. However, whether TSH influences hepatic PCSK9 expression and LDL-c metabolism remains unclear. Methods First, the correlation between TSH and lipid profiles were investigated in euthyroid population and in subclinical hypothyroidism patients. Then, an in vitro study was conducted to validate the effects of TSH on hepatic PCSK9 expression in HepG2 cells. Results Serum TSH concentrations positively correlated with LDL-c levels in euthyroid subjects. Subclinical hypothyroidism patients with higher serum TSH levels showed significantly increased serum PCSK9 levels than the matched euthyroid participants (151.29 (89.51–293.03) vs. 84.70 (34.98–141.72) ng/ml, P  Conclusion We conclude a regulating role of TSH on hepatic PCSK9 expression, which further contributing to a higher LDL-c level.