Pregnancies are a critical window period for environmental influences over the mother and the offspring. There is a growing body of evidence associating indoor and outdoor air pollution exposure to adverse pregnancy outcomes such as preterm birth and hypertensive disorders of pregnancy. Particulate matter (PM) could trigger oxi-inflammation and could also reach the placenta leading to placental damage with fetal consequences. The combination of strategies such as risk assessment, advise about risks of environmental exposures to pregnant women, together with nutritional strategies and digital solutions to monitor air quality can be effective in mitigating the effects of air pollution during pregnancy.

Preeclampsia (PE) is a pregnancy-specific disorder that affects 3 to 5% of pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and mortality. Nevertheless, how these events occur remains unclear. We hypothesized that the induction of hypoxic conditions in vitro in primary human trophoblast cells would mimic several characteristics of PE found in vivo. We applied and characterized a model of primary cytotrophoblasts isolated from healthy pregnancies that were placed under different oxygen concentrations: ambient O₂ (5% pCO₂, 21%pO₂, 24 h, termed “normoxia”), low O₂ concentration (5% pCO₂, 1.5% pO₂, 24 h, termed “hypoxia”), or “hypoxia/reoxygenation” (H/R: 6 h intervals of normoxia and hypoxia for 24 h). Various established preeclamptic markers were assessed in this cell model and compared to placental tissues obtained from PE pregnancies. Seventeen PE markers were analyzed by qPCR, and the protein secretion of soluble fms-like tyrosine kinase 1 (sFlT-1) and the placenta growth factor (PlGF) was determined by ELISA. Thirteen of seventeen genes associated with angiogenesis, the renin–angiotensin system, oxidative stress, endoplasmic reticulum stress, and the inflammasome complex were susceptible to H/R and hypoxia, mimicking the expression pattern of PE tissue. In cell culture supernatants, the secretion of sFlT-1 was increased in hypoxia, while PlGF release was significantly reduced in H/R and hypoxia. In the supernatants of our cell models, the sFlT-1/PlGF ratio in hypoxia and H/R was higher than 38, which is a strong indicator for PE in clinical practice. These results suggest that our cellular models reflect important pathological processes occurring in PE and are therefore suitable as PE in vitro models.

Preeclampsia (PE) is a complex pregnancy syndrome characterized by hypertension with or without proteinuria, affecting 2–6% of pregnancies globally. PE is characterized by excessive release of damage-associated molecular patterns (DAMPs) into the maternal circulation. This DAMP-rich milieu acts on innate immune cells, inducing a proinflammatory state characterized by elevated cytokines such as IL-1β and IL-18. This proinflammatory state in the mother and placenta results in the endothelial dysfunction strongly associated with cardiovascular disorders. While the immediate maternal and fetal risks of PE are well-documented, accumulating evidence indicates that PE also confers long-term cardiovascular risks to the mother, including hypertension, coronary heart disease, stroke, and heart failure. The underlying mechanisms connecting PE to these chronic cardiovascular conditions remain unclear. This article explores the potential role of trained innate immunity (TRIM) as a mechanistic link between PE and increased long-term cardiovascular risk. We propose that the persistent exposure to DAMPs during PE may epigenetically reprogram maternal innate immune cells and their progenitors, leading to TRIM. This reprogramming enhances the inflammatory response to subsequent stimuli, potentially contributing to endothelial dysfunction and chronic inflammation that predispose women to cardiovascular diseases later in life. Understanding the role of TRIM in PE could provide novel insights into the pathophysiology of PE-related cardiovascular complications and identify potential targets for therapeutic intervention. Further research is warranted to investigate the epigenetic and metabolic alterations in innate immune cells induced by PE and to determine how these changes may influence long-term maternal cardiovascular health.

Angiogenesis is a key process by which new capillary blood vessels are formed, sustaining the supply of oxygen and other nutrients to the body allowing its growth and wound healing, among others. However, angiogenesis also associates with pathological processes, such us tumor growth. Vascular endothelial cells produce different matrix remodeling enzymes such as matrix metalloproteinases and a-disintegrin and metalloproteinases, which have both positive and negative effects on angiogenesis, regulating the cell environment and signaling. However, little is known about the regulation of the activity of these proteases during vascular development. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a membrane-anchored inhibitor of different matrix metalloproteinases and a-disintegrin and metalloproteinases, being a critical regulator of extracellular matrix remodeling and signaling pathway, particularly Notch, which is critical for the maturation of the growing vessels. Reck knockout mice die in utero showing vascular developmental defects and massive hemorrhages. These defects were not observed in knockout mice for secreted-soluble matrix metalloproteinase inhibitors pointing to an exclusive role of RECK in vascular development and maturation since its location at the plasma membrane. Despite the above, the exact role of RECK in this process has not been clarified. This review is focused to summarize the available information on the role of RECK as membrane anchored matrix metalloproteinases and a-disintegrin and metalloproteinases inhibitor, proposing a hypothesis by which RECK play key roles in the physiology and pathophysiology of the angiogenesis processes.