Matrix metalloproteinases and their association with preeclampsia/eclampsia with maternal age: A potential link to cardiovascular disease in later life.

Maternal age is a well established risk factor for preeclampsia and eclampsia, with advanced maternal age (>35 years) associated with a significantly increased risk of developing these disorders. Preeclampsia and eclampsia are 2 of the most severe and life-threatening complications of pregnancy, affecting approximately 2%-8% of pregnancies worldwide. These disorders are characterized by high blood pressure, proteinuria, and multiorgan dysfunction, which can lead to maternal and fetal morbidity and mortality if left untreated. Despite advances in medical technology and prenatal care, the etiology of preeclampsia and eclampsia remains poorly understood, and there is a pressing need for the identification of novel biomarkers and therapeutic targets. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have a functional role in the degradation and remodeling of the extracellular matrix. MMP expression and activity changes in women with preeclampsia and eclampsia. For example, MMP-2 and MMP-9 have been shown to be elevated in the serum and placenta of women with preeclampsia, whereas MMP-1 and MMP-3 have been found to be decreased. These changes in MMP expression and activity may contribute to the development of preeclampsia and eclampsia by promoting inflammation, endothelial dysfunction, and vascular remodeling. The dysregulation of MMPs in preeclampsia/eclampsia can lead to the breakdown of the maternal-fetal interface, resulting in the release of proinflammatory cytokines and the activation of immune cells. Addressing MMP dysfunction in preeclampsia and eclampsia requires a multifaceted approach, combining pharmacological interventions, genetic insights, and a focus on oxidative stress to improve maternal and fetal health outcomes. SIGNIFICANCE STATEMENT: This study highlights the critical role of maternal age and matrix metalloproteinases (MMPs) in preeclampsia and eclampsia, severe pregnancy complications with high morbidity and mortality. Advanced maternal age increases risk, whereas dysregulated MMPs contribute to inflammation, endothelial dysfunction, and vascular remodeling, disrupting the maternal-fetal interface. Understanding MMP alterations offers potential for novel biomarkers and therapeutic targets, aiming to improve outcomes through integrated pharmacological and genetic approaches addressing immune and oxidative stress pathways.