Acute Atherosis Lesions at the Fetal-Maternal Border: Current Knowledge and Implications for Maternal Cardiovascular Health

Abstract

Decidua basalis, the endometrium of pregnancy, is an important interface between maternal and fetal tissues, made up of both maternal and fetal cells. Acute atherosis is a uteroplacental spiral artery lesion. These patchy arterial wall lesions containing foam cells are predominantly found in the decidua basalis, at the tips of the maternal arteries, where they feed into the placental intervillous space. Acute atherosis is prevalent in preeclampsia and other obstetric syndromes such as fetal growth restriction. Causal factors and effects of acute atherosis remain uncertain. This is in part because decidua basalis is challenging to sample systematically and in large amounts following delivery. We summarize our decidua basalis vacuum suction method, which facilitates tissue-based studies of acute atherosis. We also describe our evidence-based research definition of acute atherosis. Here, we comprehensively review the existing literature on acute atherosis, its underlying mechanisms and possible short- and long-term effects. We propose that multiple pathways leading to decidual vascular inflammation may promote acute atherosis formation, with or without poor spiral artery remodeling and/or preeclampsia. These include maternal alloreactivity, ischemia-reperfusion injury, preexisting systemic inflammation, and microbial infection. The concept of acute atherosis as an inflammatory lesion is not novel. The lesions themselves have an inflammatory phenotype and resemble other arterial lesions of more extensively studied etiology. We discuss findings of concurrently dysregulated proteins involved in immune regulation and cardiovascular function in women with acute atherosis. We also propose a novel hypothesis linking cellular fetal microchimerism, which is prevalent in women with preeclampsia, with acute atherosis in pregnancy and future cardiovascular and neurovascular disease. Finally, women with a history of preeclampsia have an increased risk of premature cardiovascular disease. We review whether presence of acute atherosis may identify women at especially high risk for premature cardiovascular disease.

Preeclampsia and Fetal Growth Restriction as Risk Factors of Future Maternal Cardiovascular Disease—A Review

“…The novel hypothesis links cellular fetal microchimerism (cFMC) with acute atherosis and the future development of CVD [ 48 ]. cFMC arises when cells of fetal origin are released into maternal blood and tissues during pregnancy [ 48 ].…”

“…The novel hypothesis links cellular fetal microchimerism (cFMC) with acute atherosis and the future development of CVD [ 48 ]. cFMC arises when cells of fetal origin are released into maternal blood and tissues during pregnancy [ 48 ]. These cells are known to possess stem cell-like properties, with the potential to differentiate into endothelial cells, smooth muscle cells, or leukocytes, and may persist in maternal circulation for decades [ 49 ].…”

“…It is hypothesized that in the dysfunctional placenta, fetal cells transfer more freely into the maternal bloodstream and induce a maternal anti-fetal immune response towards the fetal cells expressing foreign HLA surface peptides. If fetal cells persist in the circulation or are engrafted in maternal endothelial cells, they could induce further inflammation, especially in vessel walls, and initiate the development of inflammatory arterial lesions, particularly as acute atherosis [ 48 ].…”

“…Inadequate trophoblastic invasion with the persistence of smooth muscle in the vessel walls and vascular damage results in acute atherosis and fibrinoid necrosis of vessels [ 113 , 114 ]. Moreover, cFMCs are also detected in pregnancies complicated by severe FRF combined with impaired placental perfusion [ 48 ]. Moreover, patients with previous FGR had a more severe degree of endothelial dysfunction than those with previous preeclampsia [ 115 ].…”

Dissecting the Roles of Lipids in Preeclampsia

“…Alteration in lipid concentration has been reported to be a risk factor for preeclampsia [ 17 ]. In addition, the accumulation of lipids and lipoproteins in the arterial wall could induce the formation of atheroma plaques and thus promote subsequent atherosclerosis [ 18 , 19 ]. Preeclampsia is associated with increased concentrations of triglycerides (TGs) and remnant cholesterol in early pregnancy [ 20 ].…”