Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy

Abstract

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.

Keywords: ASC; NLRP3 inflammasome; caspases; chronic venous disease (CVD); interleukin IL-1β; placenta.

Figure 1

(A) NLRP3 mRNA expression in women with CVD and HC (*** p < 0.0001). (B) IRS scores for NLRP3 expression in the placental villi of the CVD and HC groups (C,D) (*** p < 0.0001). Images showing immunostaining for NLRP3 in the placental villi of the CVD and HC.

Figure 2

(A) ASC mRNA expression in women with CVD and HC (*** p < 0.0001). (B) IRS scores for ASC expression in the placental villi of the CVD and HC groups (C,D) (*** p < 0.0001). Images showing immunostaining for ASC in the placental villi of the CVD and HC.

Figure 3

(A) Caspase-1 mRNA expression in women with CVD and HC (** p = 0.0014). (B) IRS scores for caspase-1 expression in the placental villi of the CVD and HC groups (C,D) (* p = 0.0187). Images showing immunostaining for caspase-1 in the placental villi of the CVD and HC.

Figure 4

(A) IL-1β mRNA expression in women with CVD and HC (*** p < 0.0001). (B) IRS scores for IL-1β expression in the placental villi of the CVD and HC group (C,D) (*** p < 0.0001). Images showing immunostaining for IL-1β in the placental villi of the CVD and HC.

Figure 5

(A) Caspase-5 mRNA expression in women with CVD and HC (** p = 0.0013). (B) IRS scores for caspase-5 expression in the placental villi of the CVD and HC groups (C,D) (** p = 0.0010). Images showing immunostaining for caspase-5 in the placental villi of the CVD and HC.

Figure 6

(A) Caspase-8 mRNA expression in women with CVD and HC (*** p < 0.0001). (B) IRS scores for caspase-8 expression in the placental villi of the CVD and HC groups (C,D) (** p = 0.0019). Images showing immunostaining for caspase-8 in the placental villi of the CVD and HC.