Increased fibulin-1 plasma levels in polycystic ovary syndrome (PCOS) patients: possible contribution to the link between PCOS and cardiovascular risk

Scarinci, Elisa; Tropea, Anna; Russo, Giulio; Notaristefano, G; Messana, Calogero; Alesiani, Ornella; Fabozzi, Sm; Lanzone, Antonio; Apa, Rosanna

doi:10.1007/s40618-018-0891-3

Cited by 9 publications

(3 citation statements)

References 46 publications

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“…Fibulin-1 mRNA and protein is expressed at high level in the placenta, according to tissuespecific oligonucleotide arrays using human and mouse samples [4]. In addition to roles in the differentiation of heart, skeletal, and neuronal structures in the early human embryo, fibulin-1 is associated with a variety of conditions [5,6], including cancer, cardiovascular events, impaired kidney function [7], diabetes [7] and polycystic ovary syndrome [8]. Higher plasma levels of fibulin-1 have been observed in women with severe pre-eclampsia (PE), compared to healthy, gestational age-matched controls [9].…”

Section: Introductionmentioning

confidence: 99%

Plasma fibulin-1 levels during pregnancy and delivery: a longitudinal observational study

Orvik

Andersen

Pedersen

et al. 2021

BMC Pregnancy Childbirth

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Background Fibulin-1 is an extracellular matrix protein expressed at high levels in the placenta. Elevated circulating fibulin-1 have been observed in women with severe pre-eclampsia, whereas low levels have been found in the fetal membranes, prior to membrane rupture. The aim of the study was primarily to evaluate plasma fibulin-1 during expected normal pregnancy and delivery, and secondarily to explore fibulin-1 levels in women developing pre-eclampsia or preterm premature rupture of fetal membranes (PPROM). Methods From the historical longitudinal cohort originally consisting of 801 healthy Danish women with a singleton pregnancy, 128 women (632 samples) were selected. Of these, 107 women had normal pregnancies, nine experienced PPROM, and 12 pre-eclampsia. All samples were analyzed for fibulin-1, and levels were compared with blood donors. Differences in mean fibulin-1 between groups were estimated using a linear mixed model. Results The mean concentration of fibulin-1 in 120 blood donors was 15.7 µg/mL, (25th-75th-percentiles, 12.3–18.2), with no significant difference in groups stratified by gender or age. Compared to baseline levels in week 12–20, fibulin-1 levels increased significantly from week 29–34 (estimated difference, 5.6 µg/mL; standard error, 1.7; p < 0.001) and 35–42 (12.5 µg/mL; 1.6; p < 0.001) and normalized after birth. The decrease at delivery tended to be more pronounced after elective (-7.0 µg/mL; 2.3; p = 0.002) and emergency (-5.6 µg/mL; 2.9; p = 0.05) cesarean section than after vaginal delivery (reference group). Women who developed PPROM had lower fibulin-1 levels throughout their pregnancies (-11.6 µg/mL; 4.2; p = 0.006). We did not observe a correlate between late pre-eclampsia and fibulin-1 (-0.2 µg/mL; 3.0; p = 0.9). Conclusions Fibulin-1 was above non-pregnant levels at week 12 and increased significantly throughout pregnancy. We observed an association between low levels of fibulin-1 and PPROM. Further studies are needed to examine if fibulin-1 could serve as biomarker for the risk of PPROM. However, its role in late preeclampsia is doubtful. Trial registration The study was conducted in accordance with the Declaration of Helsinki. The participants provided written informed consent, including storage for future use. The study was approved on July 18, 2005 by The Danish National Committee on Bioethics (No. KA 05065 and S-20,090,061) and the Danish Data Protection Agency.

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Section: Introductionmentioning

confidence: 99%

Plasma fibulin-1 levels during pregnancy and delivery: a longitudinal observational study

Orvik

Andersen

Pedersen

et al. 2021

BMC Pregnancy Childbirth

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“…5 Furthermore, the PCOS is associated with significantly higher AMH levels than normal ovulatory women. 6,7 In addition, a possible association between PCOS, high AMH, and cardiovascular risk has been recently questioned. 7 Even more intriguing, an associated between PCOS and breast cancer has been suggested.…”

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confidence: 99%

“…6,7 In addition, a possible association between PCOS, high AMH, and cardiovascular risk has been recently questioned. 7 Even more intriguing, an associated between PCOS and breast cancer has been suggested. 8 PCOS may raise a woman's risk of developing uterine cancer 10-folds and breast cancer almost two folds.…”

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confidence: 99%

Anti‐Mullerian hormone and breast cancer risk—is the correlation possibly associated with the PCOS?

Blumenfeld

2018

Intl Journal of Cancer

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Dear Editor, Ge et al. 1 have recently found an association between high circulating Anti Mullerian Hormone (AMH) levels and breast cancer. The authors tested this correlation by conducting nested case-control studies within ten different cohorts, and found that breast cancer risk increased along with increasing AMH concentration, confirming this hormone as a possible biomarker for breast cancer. 1 The authors cite previous laboratory experiments whereby AMH stimulated apoptosis and reduced breast tumor growth, suggesting a protective role. [2][3][4] This apparent controversy seems intriguing, and the authors suggest that additional mechanisms may be at play. 1 The polycystic ovarian syndrome (PCOS) is the most prevalent endocrinopathy in premenopausal women, ranging from 5% to 10% and is associated with oligo-amenorrhea, infertility, fewer deliveries, and shorter lactation periods compared to a control population. 5 Furthermore, the PCOS is associated with significantly higher AMH levels than normal ovulatory women. 6,7 In addition, a possible association between PCOS, high AMH, and cardiovascular risk has been recently questioned. 7 Even more intriguing, an associated between PCOS and breast cancer has been suggested. 8 PCOS may raise a woman's risk of developing uterine cancer 10-folds and breast cancer almost two folds. 8 The adjusted hazard ratio (HR) of uterine cancer and breast cancer in subjects with PCOS were higher than that of the controls, (HR: 8.42 [95% confidence interval: 1.62-43.89] and HR: 1.99 [95% confidence interval: 1.05-3.77], respectively). 8 Others have also found 2.74-increased odd ratios for breast cancer in premenopausal PCOS subjects (95% CI 1.13-6.63).

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Relationship between the Plasma Fibulin-1 Levels, Pulse Wave Velocity, and Vascular Age in Asymptomatic Hyperuricemia

et al. 2021

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Increased fibulin-1 plasma levels in polycystic ovary syndrome (PCOS) patients: possible contribution to the link between PCOS and cardiovascular risk

Cited by 9 publications

References 46 publications

Plasma fibulin-1 levels during pregnancy and delivery: a longitudinal observational study

Plasma fibulin-1 levels during pregnancy and delivery: a longitudinal observational study

Anti‐Mullerian hormone and breast cancer risk—is the correlation possibly associated with the PCOS?

Relationship between the Plasma Fibulin-1 Levels, Pulse Wave Velocity, and Vascular Age in Asymptomatic Hyperuricemia

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