Patji Alnæs-Katjavivi

Acute atherosis in vacuum suction biopsies of decidua basalis: An evidence based research definition

BACKGROUND Acute atherosis (AA) of the uteroplacental spiral arteries has been characterised by subendothelial lipid-laden foam cells, perivascular leukocyte infiltrates (PVI) and fibrinoid necrosis. Because precise diagnostic criteria are not available for comparative research studies we developed and tested new simplified criteria based on 237 cases. METHODS Decidual basalis samples were collected by vacuum suction at elective cesarean deliveries. Spiral arteries were evaluated in serial decidual tissue sections from women with normal pregnancy, preeclampsia, and diabetes. Features of AA were sought in parallel sections stained with H&E and immunostained for CD68, cytokeratin CK7 and desmin, and costained with Periodic Acid Schiff (PAS). RESULTS Foam cell lesions were defined as two or more adjacent, intramural, vacuolated CD68 positive cells, PVI as a focal perivascular lymphocyte accumulation, more dense than in the surrounding decidua. Increased fibrinoid (PAS positive) was identified if present in ≥75% of the arterial wall circumference. PVI and increased fibrinoid were significantly associated with preeclampsia but not specifically associated with the presence of foam cell lesions. Hence we diagnosed decidua basalis AA lesions solely by the presence of foam cell lesions, occurring in preeclampsia (37%), diabetes (10%) and healthy normotensive women (11%). The simplified criterion was reproducible by different investigators. Decidua basalis AA occurred most commonly and extensively in preeclampsia, but did not distinguish between preterm and term disease. DISCUSSION Our evidence based criterion for decidua basalis AA diagnosis in vacuum suction biopsies may not apply to myometrial or decidua parietalis arteries. In decidual basalis samples it should facilitate comparisons between research studies, to improve pathophysiological understanding of AA and preeclampsia.

Natural killer cell reduction and uteroplacental vasculopathy

Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum–treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum–treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth.

The combination of maternal KIR-B and fetal HLA-C2 is associated with decidua basalis acute atherosis in pregnancies with preeclampsia

Acute atherosis is an arterial lesion most often occurring in pregnancies complicated by preeclampsia, a hypertensive pregnancy disorder. Acute atherosis predominates in the maternal spiral arteries in the decidua basalis layer of the pregnant uterus. This layer forms the fetal-maternal immunological interface, where fetal extravillous trophoblasts interact with maternal immune cells to promote decidual spiral artery remodeling and maternal immune tolerance towards the fetus. Of the classical polymorphic class I HLAs, extravillous trophoblasts express only HLA-C. HLA-C is a ligand for killer immunoglobulin-like receptors (KIR) on NK- and T-cells. Genetic combinations of fetal HLA-C and maternal KIRs affect pregnancy outcome. However, the role of HLA and KIR genes in acute atherosis is unknown. We hypothesized that specific genetic combinations of fetal HLA and maternal KIR are associated with the presence of acute atherosis lesions in the decidua basalis. We genotyped HLA class-I and II loci in paired fetal and maternal DNA samples from 166 pregnancies (83 preeclamptics, 83 controls). Acute atherosis was identified in 38 of these. Maternal KIR-loci were also genotyped. We found that the combination of maternal KIR-B haplotype and fetal HLA-C2 was significantly associated with acute atherosis in preeclampsia. In preeclamptic pregnancies with acute atherosis, 60% had this combination, compared to 24.5% in those without acute atherosis (p = 0.001). We suggest that interactions between fetal HLA-C2 and activating KIRs on maternal decidual NK-cells or T-cells may contribute to the formation of acute atherosis by promoting local decidual vascular inflammation.

Auto-antibodies against the angiotensin II type I receptor in women with uteroplacental acute atherosis and preeclampsia at delivery and several years postpartum

BACKGROUND Uteroplacental acute atherosis is a pregnancy-specific lesion resembling early stages of atherosclerosis found frequently in preeclampsia. Preeclampsia is associated with an increased risk for future maternal atherosclerotic cardiovascular disease. The renin-angiotensin-system plays a role both in atherosclerosis and in preeclampsia. Circulating agonistic autoantibodies at the angiotensin-II type 1 receptor (AT1-AA) are increased in preeclampsia. We hypothesized an association between AT1-AA at delivery and postpartum with acute atherosis in pregnancy. MATERIAL AND METHODS Maternal serum and decidua basalis tissue was collected at elective cesarean section (n = 41; 24 preeclampsia, 17 normotensive controls). Circulating AT1-AA were detected by a bioassay using spontaneously beating rat cardiomyocytes at delivery (n = 41) and 5-8 years postpartum in a subgroup (n = 10). Decidual acute atherosis was assessed by immunohistochemistry. RESULTS Significantly less normotensive controls (18%; 3/17) than women with preeclampsia (58%; 14/24) were AT1-AA positive at delivery, p<0.01. Uteroplacental acute atherosis and circulating AT1-AA at delivery were not significantly correlated. Postpartum, 2 prior preeclamptic women had circulating AT1-AA, both without acute atherosis in pregnancy. CONCLUSIONS Our results confirm that circulating AT1-AA are present significantly more often in preeclampsia than in normotensive pregnancy, however without association to acute atherosis. Whether circulating maternal AT1-AA or acute atherosis target young women at increased long-term cardiovascular risk warrants further investigations.

Corrigendum to “Acute atherosis in vacuum suction biopsies of decidua basalis: An evidence based research definition” [Placenta 37C (2016) 26–33]

Corrigendum to “Acute atherosis in vacuum suction biopsies of decidua basalis: An evidence based research definition” [Placenta 37C (2016) 26e33] Patji Alnaes-Katjavivi , Fiona Lyall , Borghild Roald , Christopher W.G. Redman , Anne Cathrine Staff a, * a Department of Obstetrics and Department of Gynecology, Oslo University Hospital, Ullevål and Faculty of Medicine, University of Oslo, Norway b University of Glasgow, School of Medicine, Glasgow, UK c Department of Pathology, Oslo University Hospital, Ullevål and Faculty of Medicine, University of Oslo, Norway d Department of Obstetric Medicine, University of Oxford, Oxford, UK