» Articles » PMID: 29485737

Hypertension in Pregnancy: Taking Cues from Pathophysiology for Clinical Practice

Overview
Journal Clin Cardiol
Date 2018 Feb 28
PMID 29485737
Citations 23
Authors
Affiliations
Soon will be listed here.
Abstract

Pregnancy-related hypertension (PHTN) syndromes are a frequent and potentially deadly complication of pregnancy, while also negatively impacting the lifelong health of the mother and child. PHTN appears in women likely to develop hypertension later in life, with the stress of pregnancy unmasking a subclinical hypertensive phenotype. However, distinguishing between PHTN and chronic hypertension is essential for optimal management. Preeclampsia (PE) is linked to potentially severe outcomes and lacks effective treatments due to poorly understood mechanisms. Inadequate remodeling of spiral uterine arteries (SUAs), the cornerstone of PE pathophysiology, leads to hypoperfusion of the developing placenta. In normal pregnancies, extravillous trophoblast (EVT) cells assume an invasive phenotype and invade SUAs, transforming them into large conduits. Decidual natural killer cells play an essential role, mediating materno-fetal immune tolerance, inducing early SUA remodeling and regulating EVT invasiveness. Notch signaling is important in EVT phenotypic switch and is dysregulated in PE. The hypoxic placenta releases antiangiogenic and proinflammatory factors that converge upon maternal endothelium, inducing endothelial dysfunction, hypertension, and organ damage. Hypoxia-inducible factor 1-α is upstream of such molecules, whereas endothelin-1 is a major effector. We also describe important genetic links and evidence of incomplete materno-fetal immune tolerance, with PE patients presenting with autoantibodies, lower T , and higher T 17 cells. Thus, PE manifestations arise as a consequence of mal-placentation or/and because of a predisposition of the maternal vascular bed to excessively react to pathogenic molecules. From this pathophysiological basis, we provide current and propose future therapeutic directions for PE.

Citing Articles

Association of hypertensive disorder of pregnancy with necrotizing enterocolitis in very preterm infants: A retrospective cohort study.

Chen W, Yang J, Jiang S, Lei X, Zhou L, Zhou J PLoS One. 2024; 19(11):e0313035.

PMID: 39527615 PMC: 11554212. DOI: 10.1371/journal.pone.0313035.


Persistent hypertension among postpartum women with comorbid HIV and preeclampsia in Zambia.

Mukosha M, Hatcher A, Lubeya M, Maposa I, Chi B, Mutale W PLoS One. 2024; 19(9):e0309915.

PMID: 39231156 PMC: 11373822. DOI: 10.1371/journal.pone.0309915.


Association of Phenols, Parabens, and Their Mixture with Maternal Blood Pressure Measurements in the PROTECT Cohort.

Varshavsky J, Meeker J, Zimmerman E, Woodbury M, Aung M, Rosario-Pabon Z Environ Health Perspect. 2024; 132(8):87004.

PMID: 39140735 PMC: 11323763. DOI: 10.1289/EHP14008.


Digital health technologies for high-risk pregnancy management: three case studies using Digilego framework.

Myneni S, Zingg A, Singh T, Ross A, Franklin A, Rogith D JAMIA Open. 2024; 7(1):ooae022.

PMID: 38455839 PMC: 10919928. DOI: 10.1093/jamiaopen/ooae022.


OX40 (CD134) Expression on T Regulatory Cells Is Related to Serious Hypertensive Disorders in Pregnancy.

Kwiatek M, Kojak A, Kwasniewska A J Cardiovasc Dev Dis. 2023; 10(10).

PMID: 37887878 PMC: 10607140. DOI: 10.3390/jcdd10100431.


References
1.
Smith S, Dunk C, Aplin J, Harris L, Jones R . Evidence for immune cell involvement in decidual spiral arteriole remodeling in early human pregnancy. Am J Pathol. 2009; 174(5):1959-71. PMC: 2671283. DOI: 10.2353/ajpath.2009.080995. View

2.
Bowles A, Wise R, Gerstein B, Thomas R, Ogelman R, Febbo I . Immunomodulatory Effects of Adipose Stromal Vascular Fraction Cells Promote Alternative Activation Macrophages to Repair Tissue Damage. Stem Cells. 2017; 35(10):2198-2207. DOI: 10.1002/stem.2689. View

3.
Thadhani R, Kisner T, Hagmann H, Bossung V, Noack S, Schaarschmidt W . Pilot study of extracorporeal removal of soluble fms-like tyrosine kinase 1 in preeclampsia. Circulation. 2011; 124(8):940-50. DOI: 10.1161/CIRCULATIONAHA.111.034793. View

4.
Goulopoulou S, Davidge S . Molecular mechanisms of maternal vascular dysfunction in preeclampsia. Trends Mol Med. 2014; 21(2):88-97. DOI: 10.1016/j.molmed.2014.11.009. View

5.
Bartsch E, Medcalf K, Park A, Ray J . Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies. BMJ. 2016; 353:i1753. PMC: 4837230. DOI: 10.1136/bmj.i1753. View