Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy.
María Asunción Sánchez-GilOscar Fraile-MartínezCielo García-MonteroDiego De Leon-OlivaDiego Liviu BoaruPatricia De Castro-MartinezAdrían Camacho-AlcázarJuan Antonio de Leon-LuisCoral BravoRaúl Díaz-PedreroLaura López-GonzalezJulia BujánMaría J CanceloMelchor Alvarez De MonNatalio Garcia-HonduvillaMiguel A SáezMiguel Ángel OrtegaPublished in: International journal of molecular sciences (2024)
Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC-apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain-caspase 1, caspase 5, caspase 8, and interleukin 1β) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations.
Keyphrases
- nlrp inflammasome
- cell death
- oxidative stress
- polycystic ovary syndrome
- induced apoptosis
- pregnancy outcomes
- immune response
- pregnant women
- endoplasmic reticulum stress
- real time pcr
- genome wide
- cell cycle arrest
- preterm infants
- gene expression
- type diabetes
- poor prognosis
- signaling pathway
- metabolic syndrome
- single cell
- drug induced
- inflammatory response
- preterm birth
- dendritic cells
- copy number
- insulin resistance
- adipose tissue
- transcription factor