Journal
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
Volume 18, Issue 13, Pages 2814-2827Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijms.58992
Keywords
Venous insufficiency; Chronic Venous Disease; Pregnancy; IGF-1/PAPP-A/STC-2 pthaway; Wnt/beta-catenin canonical pathway
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Funding
- Instituto de Salud Carlos III (Plan Estatal de I + D+i 2013-2016) [FIS-PI18/00912]
- European Development Regional Fund A way to achieve Europe (ERDF)
- [B2017/BMD-3804 MITIC-CM]
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This study examined the genetic and protein expression in women with lower limbs venous insufficiency, revealing alterations in important pathways and factors such as IGF-1/PAPP-A/STC-2, PI3K/Akt, Wnt/beta-catenin, and inflammatory cytokines. These results contribute to the understanding of the association between venous insufficiency and placental damage, highlighting abnormal tissue environment and cellular regulation.
Lower limbs venous insufficiency refers to a wide variety of venous disorders grouped by the term of chronic venous disease (CVD). Hemodynamic and hormonal changes related to pregnancy period, may promote the development of CVD affecting approximately 1 in 3 women. It has been shown that the presence of this condition is associated with damage and placental suffering. Thus, taking IGF-1/PAPP-A/STC-2, inflammatory cytokines production, PI3K/Akt and Wnt/beta-catenin pathways as a part of the alterations that occurs in the placenta due to CVD, the aim of this study will be to examine the main components of these pathways. Genic and protein expression of PAPP-A, STC-2, IGF-1, IRS-4 Wnt-1, beta-catenin, c-myc, Cyclin D1, IL-4/IL-6 and PI3K/Akt/mTOR pathway will be analysed through RT-qPCR and immunohistochemical techniques in women with CVD (n=62) and pregnant women without this condition (HC) (n= 52). PAPP-A, IGF-1, IL-4, IL-6, IRS-4, PI3K, Akt, mTOR, Wnt-1, beta-catenin, c-myc and Cyclin D1 expression were found to be increased in women with CVD, whereas STC-2 were decreased in this group, compared to non-affected women. Our study has demonstrated that IGF-1/PAPP-A/STC-2 axis, PI3K/Akt and Wnt/beta-catenin pathways, along with c-myc, Cyclin D1 and inflammatory cytokines are altered in placenta women with CVD. These results extent the knowledge that CVD is associated to a placenta damage with abnormal tissue environment and cellular regulation.
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