Effect of urotensin II on apolipoprotein B ₁₀₀ and apolipoprotein A-I expression in HepG2 cell line

Abstract

Background:Increased apolipoprotein B100 (apo B) and decreased apolipoprotein A-I (apo A-I) production are important risk factors in atherosclerosis. Urotensin II (UII), as the most potent vasoconstrictor in human, is related with hypertension and probably atherosclerosis. Because of the relationship between the hypertension and lipoprotein metabolism in atherosclerosis, the aim of this study was to test the effect of urotensin II on apo B and apo A-I expression in hepatic (HepG2) cell line.Materials and Methods:HepG2 cells were treated with 10, 50, 100, and 200 nmol/L of urotensin II (n = 6). Relative apo B and apo A-I messenger RNA (mRNA) levels in conditioned media, normalized to glyceraldehyde-3-phosphate dehydrogenase, were measured with quantitative real-time polymerase chain reaction method. In addition, apo B and apo A-I levels were also estimated and compared with the controls using the western blotting method. Data were analyzed statistically by ANOVA and non-parametric tests.Results:The apo B mRNA levels were not increased significantly following the treatment with UII. However, apo B protein levels were increased significantly after the treatment with urotensin II, especially at 100 and 200 nmol/L. The apo A-I mRNA and protein levels in conditioned media also were not significantly changed. However, there was a significant decrease in apo A-I mRNA and protein levels at 200 nM UII.Conclusions:UII might increase apo B at protein level probably through participating factors in its synthesis and/ or stability/degradation. In addition, UII may have decreasing effect at more than 200 nM concentrations on apo A-I.

Urotensin II: an inflammatory cytokine

“…Reports in recent years show that UII can induce the expression and secretion of various inflammatory cytokines, such as MCP-1 and TGF-β, causing arterial inflammatory injury (You et al 2012. UII can also induce apolipoprotein apoB expression and suppress apoA-1 expression, promoting the development of atherosclerosis (Khoshi et al 2014). In addition, UII can promote the proliferation of VSMC to lead to vascular stenosis and remodeling, by activating the ERK/ROS signaling pathway in atherosclerotic lesions (Kim et al 2017).…”