# New Frontiers in the Pathophysiology of Hypertensive Pregnancy Disorders: A Systematic Review of Molecular Insights into Preeclampsia

## TL;DR

This systematic review explores recent molecular insights into preeclampsia, a hypertensive disorder during pregnancy, highlighting key mechanisms like angiogenesis and immune responses.

## Contribution

The paper systematically summarizes novel molecular mechanisms and their interplay in preeclampsia pathophysiology.

## Key findings

- Angiogenetic dysregulation and endothelial injury are prominent mechanisms in preeclampsia.
- Oxidative imbalance and immune-inflammatory responses are frequently observed molecular pathways.
- Epigenetic and non-coding RNA regulation contribute to placental dysfunction in preeclampsia.

## Abstract

Background: Hypertensive disorders during pregnancy (HDP) pose a significant health risk to both mothers and infants. Despite extensive research, the precise pathophysiology of preeclampsia remains elusive, posing a formidable challenge to clinicians and researchers alike. This systematic review aims to summarize recent advances in understanding PE pathophysiology with particular emphasis on molecular mechanisms involved, as well as the roles and effects of genetics and hormones in PE. Methods: The literature was searched to identify clinical research investigating the underlying molecular and cellular mechanisms of PE, along with the genetic, hormonal, and pathophysiological changes. All studies were solicited from the databases PubMed, Scopus, and ScienceDirect according to the PRISMA 2020 workflow. The eligibility criteria were developed using the PECO (Population, Exposure, Comparator, Outcome) framework. Results: The most common molecular mechanisms found were: angiogenetic dysregulation and endothelial injury mechanism (n = 17), oxidative/redox imbalance and mitochondrial dysfunction mechanisms (n = 14), immune, inflammatory, and complement mechanisms (n = 13), trophoblast invasion, differentiation, and placental remodeling mechanism (n = 13), epigenetic and non-coding RNA regulation mechanisms (n = 9). Most of the included articles demonstrate more than one molecular mechanism, and the total number for each mechanism reflects the extent to which it is demonstrated in the studies. Conclusion: The complex development of hypertensive pregnancy disorders reflects numerous molecular mechanisms implicated in this process. From genetic and environmental influences on placental dysfunction to epigenetic changes and systemic dysregulation, each mechanism contributes to health outcomes for both the mother and the child.