Effect of heme oxygenase 1 and renin/prorenin receptor on oxidized low-density lipoprotein-induced human umbilical vein endothelial cells

摘要

The incidence of depression has previously been correlated to hypertension. The aim of the present study was to explore the mechanisms of depression and hypertension by examining the expression and interaction of renin/prorenin receptor (PRR) and heme oxygenase 1 (HO-1) in vascular endothelial cells. A case-control study was conducted, and general data and serum factors were compared between hypertension patients complicated with depression and patients with hypertension alone. Logistic regression analysis was used to detect risk factors associated with hypertension complicated with depression. In addition, human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) and/or PRR gene silencing, and a Cell Counting Kit-8 (CCK-8) assay was performed to test their proliferation. The concentrations of inflammatory factors and oxidative stress factor were also detected using enzyme-linked immunosorbent assay and chemical colorimetry. Western blot analysis and reverse transcription-quantitative polymerase chain reaction were applied to detect protein and mRNA expression levels, respectively. The results revealed that HO-1 and renin precursor (Rep) were independent factors that affected hypertension complicated with depression. Serum HO-1 levels in patients with hypertension complicated with depression were significantly lower than that in hypertensive patients without depression, while Rep levels in patients with hypertension complicated with depression were significantly higher than that in hypertensive patients without depression. In HUVECs, ox-LDL reduced the cell proliferation in a dose-dependent manner, upregulated the expression of PRR gene and downregulated the expression of HO-1 gene. It was also observed that silencing of the PRR gene promoted the expression of the HO-1 gene. Furthermore, ox-LDL upregulated the inflammatory response and oxidative stress levels, while PRR gene silencing inhibited the ox-LDL-induced inflammatory factor and oxidative stress levels in HUVECs. Thus, regulating the expression levels of HO-1 and PRR to inhibit the oxidative stress and pro-inflammatory effect of ox-LDL may provide new insight for the treatment of hypertension patients with depression.