Background Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 expression, is present in atherosclerotic-like lesions of heart transplantation and considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. Intercellular adhesion molecule-1-overexpressing-activated endothelial cells are more resistant to trophoblast displacement than nonactivated endothelium and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. Objective To determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. Study Design A cross-sectional study of 123 placentas (19-42 weeks’ gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15), and small for gestational age (n = 10) was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of intercellular adhesion molecule-1 (ICAM-1). Investigators examining microscopic sections were blinded to clinical diagnosis. Pairwise comparisons among placenta groups were performed with the Fisher’s exact and Wilcoxon rank sum tests using a Bonferroni-adjusted level of significance (.025). Results 87% (94/108) of placentas having spiral arteries with failure of physiologic transformation (actin-positive and cytokeratin-negative) in the basal plate, and 0% (0/15) of placentas having only spiral arteries with complete physiologic transformation (cytokeratin-positive and actin-negative), had arterial endothelial and/or interstitial extravillous trophoblasts reactive with the ICAM-1 activation marker (P < .001). A significant correlation (R2 = 0.84) was found between expression of spiral artery endothelial and interstitial extravillous trophoblast ICAM-1 (P < .001) in activated placentas. Lesions of atherosis were found in 31.9% (30/94) of placentas with complete and/or partial failure of physiologic transformation of spiral arteries that were ICAM-1-positive, in none of the 14 placentas with failure of physiolog...

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Background: C‐reactive protein (CRP) levels are associated with endothelial activation and development of atherosclerosis. Confirmation of this association in vivo remains controversial. Some researchers reported a pro‐atherosclerotic effect of CRP in ApoE‐deficient mice (apoE−/−) and others did not. Here we treated apoE−/− mice with azide‐ and endotoxin‐free native‐CRP (n‐CRP), then evaluated the extent of atherosclerosis. Methods and Results: Twelve‐week old male apoE−/− mice (n=22) were used. Half of the animals received a continuous infusion of n‐CRP (20.4 μg/mice/day) for four weeks using osmotic pumps; the other half CRP solvent alone. Mice were fed Purina 5001 rodent diet. Then atherosclerosis was evaluated in aortic roots after Oil Red‐O staining, and in complete aortas after Sudan IV staining. The extent of atherosclerotic lesion in the aortic root was not significantly different between the groups (CRP: 29.60 % vs. Control: 29.4 %, p= 0.967). However when measured throughout the whole aorta, the size of the lesion in mice treated with CRP was significantly lower compared to control animals (7 % vs. 9.2%, p= 0.0029). Serum levels of soluble ICAM‐1, VCAM‐1, E‐selectin and P‐selectin were not significantly different between groups (p> 0.117). Conclusions: We demonstrated that continuous infusion of human n‐CRP to apoE−/− mice did not increase atherosclerotic lesion formation, but, surprisingly, was associated with reduction of lesion formation throughout the whole aorta but not in the aortic root.

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