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

Sánchez-Gil, María Asunción; Fraile-Martinez, Oscar; García-Montero, Cielo; De Leon-Oliva, Diego; Boaru, Diego Liviu; De Castro-Martinez, Patricia; Camacho-Alcázar, Adrían; De León-Luis, Juan A.; Bravo, Coral; Díaz-Pedrero, Raúl; López-Gonzalez, Laura; Bujan, Julia; Cancelo, María J.; Álvarez-Mon, Melchor; García-Honduvilla, Natalio; Saez, Miguel A.; Ortega, Miguel A.

doi:10.3390/ijms25105528

Open AccessArticle

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

by

María Asunción Sánchez-Gil

^1,2,3,

Oscar Fraile-Martinez

^1,2

,

Cielo García-Montero

^1,2,

Diego De Leon-Oliva

^1,2,

Diego Liviu Boaru

^1,2,

Patricia De Castro-Martinez

^1,2,

Adrían Camacho-Alcázar

¹,

Juan A. De León-Luis

^4,5

,

Coral Bravo

^4,5,

Raúl Díaz-Pedrero

^2,6

,

Laura López-Gonzalez

^2,7,

Julia Bujan

^1,2

,

María J. Cancelo

^6,8

,

Melchor Álvarez-Mon

^1,2,9

,

Natalio García-Honduvilla

^1,2

,

Miguel A. Saez

^1,2,7,†

and

Miguel A. Ortega

^1,2,*,†

¹

Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain

²

Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain

³

University Defense Center of Madrid (CUD), 28047 Madrid, Spain

⁴

Department of Obstetrics and Gynecology, University Hospital Gregorio Marañón, 28009 Madrid, Spain

⁵

Health Research Institute Gregorio Marañón, 28009 Madrid, Spain

⁶

Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain

⁷

Pathological Anatomy Service, University Hospital Gómez-Ulla, 28806 Alcala de Henares, Spain

⁸

Department of Obstetrics and Gynecology, University Hospital of Guadalajara, 19002 Guadalajara, Spain

⁹

Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Prince of Asturias, Networking Research Center on for Liver and Digestive Diseases (CIBEREHD), 28806 Alcala de Henares, Spain

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2024, 25(10), 5528; https://doi.org/10.3390/ijms25105528

Submission received: 17 April 2024 / Revised: 14 May 2024 / Accepted: 16 May 2024 / Published: 18 May 2024

(This article belongs to the Special Issue Translational Medicine of Vascular and Lymphatic Diseases: From the Molecule to the Clinic)

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

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MDPI and ACS Style

Sánchez-Gil, M.A.; Fraile-Martinez, O.; García-Montero, C.; De Leon-Oliva, D.; Boaru, D.L.; De Castro-Martinez, P.; Camacho-Alcázar, A.; De León-Luis, J.A.; Bravo, C.; Díaz-Pedrero, R.; et al. Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy. Int. J. Mol. Sci. 2024, 25, 5528. https://doi.org/10.3390/ijms25105528

AMA Style

Sánchez-Gil MA, Fraile-Martinez O, García-Montero C, De Leon-Oliva D, Boaru DL, De Castro-Martinez P, Camacho-Alcázar A, De León-Luis JA, Bravo C, Díaz-Pedrero R, et al. Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy. International Journal of Molecular Sciences. 2024; 25(10):5528. https://doi.org/10.3390/ijms25105528

Chicago/Turabian Style

Sánchez-Gil, María Asunción, Oscar Fraile-Martinez, Cielo García-Montero, Diego De Leon-Oliva, Diego Liviu Boaru, Patricia De Castro-Martinez, Adrían Camacho-Alcázar, Juan A. De León-Luis, Coral Bravo, Raúl Díaz-Pedrero, and et al. 2024. "Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy" International Journal of Molecular Sciences 25, no. 10: 5528. https://doi.org/10.3390/ijms25105528

APA Style

Sánchez-Gil, M. A., Fraile-Martinez, O., García-Montero, C., De Leon-Oliva, D., Boaru, D. L., De Castro-Martinez, P., Camacho-Alcázar, A., De León-Luis, J. A., Bravo, C., Díaz-Pedrero, R., López-Gonzalez, L., Bujan, J., Cancelo, M. J., Álvarez-Mon, M., García-Honduvilla, N., Saez, M. A., & Ortega, M. A. (2024). Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy. International Journal of Molecular Sciences, 25(10), 5528. https://doi.org/10.3390/ijms25105528

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

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