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Abstract: PO2610

Senescence Markers in Women with Preeclampsia Pregnancies

Session Information

Category: Women’s Health and Kidney Diseases

  • 2000 Women’s Health and Kidney Diseases

Authors

  • Suvakov, Sonja, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Ghamrawi, Ranine, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Tu, Haitao, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
  • White, Wendy, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Milic, Natasa, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Grande, Joseph P., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Garovic, Vesna D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

Preeclampsia, a hypertensive disorder of pregnancy, is characterized by impaired angiogenesis and inflammation. Data indicate that preeclampsia is mechanistically related to cellular senescence, an irreversible cell-arrest mechanism which has been increasingly associated with accelerated aging. The aim of this study was to determine if senescence plays a role in the pathophysiology of preeclampsia. To that end, we compared SASP components in blood and fat tissue sections between preeclamptic and normotensive pregnancies, as well as p21 and p16 expression in the fat and kidney tissue samples.

Methods

Blood samples from preeclamptic and normotensive patients at the time of delivery were used to study circulating senescence-associated secretory phenotype (SASP) components. Plasma SASP components were tested using Luminex 200 system. Fat tissue explants (3-5 g) were obtained during the surgery from pregnant women who were clinically indicated for C-section. Kidney sections originated from the autopsy material from patients who died from preeclampsia. Upon protein isolation from fat tissue, SASP components were measured. Fat and kidney tissue sections were immunostained for p16 and p21. Preeclamptic and normotensive participants were matched for age and BMI.

Results

Significant increase of senescence markers were found in blood of preeclamptic pregnancies for NGF (1.30±0.82 vs. 0.77±0.19, p=0.032), MCP1 (316.95±163.95 vs. 207.53±84.78, p=0.047), TNFa (2.79±1.08 vs. 2.06±0.64, p=0.043) and Pai1 (58.03±18.85 vs. 38.12±20.86, p=0.023). Similarly, significant increase in senescence markers was found in preeclamptic pregnancies for MCP1 and TNFa. Expression of p16 was significantly increased in fat tissue, whereas the difference in p21 expression between preeclamptic and normotensive patients was not observed. Expression of p16 in preeclamptic renal sections was significantly higher (p=0.02) than in sections from normotensive pregnancies. The p21 expression did not differ between preeclamptic and normotensive kidney sections.

Conclusion

Women with preeclampsia have higher senescent burden compared to normotensive pregnant women at the time of delivery. Senolytic agents that target senescence may offer the opportunity for mechanisam-based therapies.

Funding

  • NIDDK Support