Evidence that atherosis of the spiral artery represents atherosclerotic lesions similar to those of native and transplant-induced atherosclerosis: implications for understanding the pathophysiology of obstetrical syndromes and long-term cardiovascular risk.

BackgroundMothers who experience major obstetrical syndromes (ie, preeclampsia, spontaneous preterm birth, fetal growth restriction, fetal death, and gestational diabetes mellitus) are at an increased risk for early death from cardiovascular disease. Atherosis of the spiral arteries has been observed in each of these syndromes. The lesion is characterized by subendothelial lipid-filled foam cells, fibrinoid necrosis, and leukocyte infiltration. We aimed to characterize the morphologic feature of the lesion using multidimensional immunohistochemistry and to determine whether atherosis has features similar to native and transplant-induced atherosclerosis.ObjectiveThe objectives of the study were (1) to identify different cell types within atherosis lesions, (2) to determine whether the lesions had a phenotypic pattern of activation and inflammation, and (3) to ascertain whether atherosis resembles the lesions observed in the coronary arteries of patients with either native or transplant-induced atherosclerosis.Study designA retrospective case-control study was performed in placentas with and without atherosis. Basal plate samples (5.6±0.9 per placenta) were studied immunohistochemically with antibodies specific for α-smooth muscle actin, cytokeratin, von Willebrand factor, fibrin (no fibrinogen), cluster of differentiation 68, cluster of differentiation 36, intercellular adhesion molecule-1/cluster of differentiation 54, human leukocyte antigen-DR, nuclear factor kappa B, and C-reactive protein. Samples from hearts with atherosclerosis, native (n=10) and transplant-induced (n=10), and without atherosclerosis (n=10) were used for comparisons. Investigators examining microscopic sections were masked to clinical diagnoses. Statistical comparisons were performed using Fisher's exact (for discrete measures) and Kruskal-Wallis (for continuous measures) tests. Comparisons of continuous measures used the Wilcoxon Rank Sum test. Analysis of variance assessed the means from subgroups.Results(1) We compared the cellular and immunopathologic features of 134 placentas with atherosis and 134 without atherosis; (2) histologic and immunopathologic analyses showed that atherotic lesions contain an average of (a) 29.4% of foam cells, (b) 30.6% of cells with lipid deposits (assessed by Oil Red O-positive cells), (c) lack intra-arterial trophoblasts, (d) 52.4% of smooth muscle cells, and (e) 30.8% of macrophages (cluster of differentiation 68-positive cells) which express the scavenger receptor cluster of differentiation 36; and (3) atherotic lesions stained positive for intercellular adhesion molecule-1 (48.4% of cells), human leukocyte antigen-DR (48% of cells), nuclear factor kappa B (endothelium and macrophages) (48.9% of cells), and C-reactive protein (17.6% of cells). Similar histopathologic and immunopathologic characteristics were identified in native and transplant-induced coronary atherosclerosis but not in control vessels.ConclusionAtherosis has similar morphologic and immunopathologic features as those observed in native and transplant-induced coronary atherosclerosis. These observations have implications in understanding the origin of atherosis and may explain why a subset of women with obstetrical syndromes is at an increased risk for cardiovascular disease later in life. We propose that the term atherosis be replaced with atherosclerosis of the spiral arteries.