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Retrospective studies and quantitative proteomics reveal that abnormal expression of blood pressure, blood lipids, and coagulation related proteins is associated with hypospadias

  • Kexin Zhang,
  • Shengxiong Wang,
  • Ying Qiu,
  • Baoling Bai,
  • Qin Zhang,
  • Xianghui Xie

摘要

Hypospadias refers to the abnormal position of the male urethral orifice, which not only leads to urination disorder but also causes sexual dysfunction in adulthood. However, the complex and diverse pathogenic factors of hypospadias are still unclear. To study the pathogenesis and prognosis of hypospadias, we counted the serological indexes of children with hypospadias, and found that sSBP, TC and LDL increased in children with mild, moderate and severe hypospadias. Subsequently, we used quantitative proteomics to find differential proteins in mild, moderate and severe hypospadias. After bioinformatics analysis and biochemical experiments on the screened DEPs, we found that the expression of proteins related to immune inflammation, coagulation, blood pressure and inflammation, and blood lipid were differential expressed in the prepuce tissue of children with hypospadias. We further confirmed that the proteins FGB, FGG, SERPINA1, and AGT involved in the angiotensin system, cholesterol metabolism, and coagulation were significantly up-regulated by biochemical experiments. In particular, the AGT protein of the angiotensin system involved in blood pressure regulation, we have shown that it increases with the severity of hypospadias. This study suggests that children with hypospadias are more likely to suffer from hyperlipidemia and cardiovascular disease (CVD). Our findings provide a theoretical basis for early monitoring of blood lipids and blood pressure to prevent CVD in children with hypospadias.

Graphical abstract

Firstly, we analyzed the serological indexes of children with hypospadias and control children. Then we took 5 samples of prepuce tissue from children with mild, moderate, severe hypospadias and control group respectively, and performed proteomics identification. After bioinformatics analysis andbiochemical experiment verification of DEPs. We found that DEPs involved in immune, inflammatory, lipid metabolism and coagulation processes were significantly increased. Finally, we used biochemical experimental techniques to verify DEPs.