Acute Atherosis Research Articles

The relation of birthweight to histological appearances in vessels of the placental bed

Summary. Biopsy of the placental bed was attempted at caesarean section in 109 patients: 77 consecutive and 32 selected because of the maternal or fetal condition. Forty‐seven (44%) of these biopsies were from the placental bed and contained spiral arteries suitable for comment. Histological examination separated the patients into four groups: comprising 11 whose vessels showed normal physiological changes, 20 who showed inadequate physiological change, 12 with acute atherosis, and four with a mixed pattern. There was no relation between these changes and maternal age, parity, race or smoking habit, but no physiological change and atherosis were more common in association with maternal hypertension. Mean adjusted birthweight was greatest in those with physiological changes, less in those without physiological changes or the mixed pattern, and least in those with atherosis. The four patients in the mixed group did not have any unifying clinical characteristics.

The relation of birthweight to histological appearances in vessels of the placental bed

Biopsy of the placental bed was attempted at caesarean section in 109 patients: 77 consecutive and 32 selected because of the maternal or fetal condition. Forty-seven (44%) of these biopsies were from the placental bed and contained spiral arteries suitable for comment. Histological examination separated the patients into four groups: comprising 11 whose vessels showed normal physiological changes, 20 who showed inadequate physiological change, 12 with acute atherosis, and four with a mixed pattern. There was no relation between these changes and maternal age, parity, race or smoking habit, but no physiological change and atherosis were more common in association with maternal hypertension. Mean adjusted birthweight was greatest in those with physiological changes, less in those without physiological changes or the mixed pattern, and least in those with atherosis. The four patients in the mixed group did not have any unifying clinical characteristics.

Maternal Vascular Lesions in Placentae of Small-for-Gestational-Age Infants

Placentae from 140 term pregnancies were studied. Seventy-four were from uncomplicated pregnancies in which the neonates were within the normal weight range for their gestational age. The remaining 66 placentae were from pregnancies whose infants were small for gestational age (SGA). In eight cases of this latter group a curettage of placental bed was performed during caesarean section. Maternal arterial vessels with absence of trophoblastic migration were observed in basal decidua and basal plate, and acute atherosis in parietal decidua, basal decidua and basal plate, all of them in cases of the SGA group. Furthermore, chronic vasculitis-like lesions were observed in the parietal decidua of three cases from the SGA group and in two others of the control group. No vascular lesions were found in cases of the control group when an infant's birthweight was above the 25th percentile of the normal ponderal range. Atheromatous-like lesions have been described in placental bed arteries in pre-eclampsia, systemic lupus erythematosus and SGA infants: this type of vasculopathy has also been described in rejection of renal transplants. Moreover, lesions similar to those found in chronic vasculitis were also described in the latter pathological entity. It is suggested that these vasculopathies may represent different steps of the same lesion. On the other hand, they may also be the expression of a maternal immunological attack on placental tissues causing a deficit of placentation, low birthweight being the consequence of this deficit.

Chronic villitis of unknown etiology and maternal arterial lesions in preeclamptic pregnancies

Placental lesions from 361 singleton full-term pregnancies were studied. These placentas were divided into two major groups: the study group consisting of 146 placentas from mothers with pregnancy-induced hypertension and a normotensive control group, which included 215 placentas from mothers with normal pregnancies. Each group was divided into three subgroups according to the allocation of infant's birthweight in the normal ponderal curve. A statistically significant higher incidence and severity of villous lesions was observed in placentas of mothers with pregnancy-induced hypertension when infants were over the 25th centile of the ponderal curve. Vascular lesions, i.e., absence of physiological changes in spiral arteries of the placental bed, acute atherosis and chronic vasculitis-like lesions were also more frequently observed in the hypertensive group than in controls. These placental lesions have been described in placentas of small for gestational age infants with or without maternal hypertension and in those of preeclamptic women with appropriate for gestational age infants. Since acute atherosis-like lesions have been reported in placentas of pregnant women with systemic lupus erythematosus and in rejected renal transplants, a possible maternal immunological reaction against fetal tissues could be responsible for the pathogenesis of these entities.

Maternal vascular lesions in placentae of small-for-gestational-age infants

Placentae from 140 term pregnancies were studied. Seventy-four were from uncomplicated pregnancies in which the neonates were within the normal weight range for their gestational age. The remaining 66 placentae were from pregnancies whose infants were small for gestational age (SGA). In eight cases of this latter group a curettage of placental bed was performed during caesarean section. Maternal arterial vessels with absence of trophoblastic migration were observed in basal decidua and basal plate, and acute atherosis in parietal decidua, basal decidua and basal plate, all of them in cases of the SGA group. Furthermore, chronic vasculitis-like lesions were observed in the parietal decidua of three cases from the SGA group and in two others of the control group. No vascular lesions were found in cases of the control group when an infant's birthweight was above the 25th percentile of the normal ponderal range. Atheromatous-like lesions have been described in placental bed arteries in pre-eclampsia, systemic lupus erythematosus and SGA infants: this type of vasculopathy has also been described in rejection of renal transplants. Moreover, lesions similar to those found in chronic vasculitis were also described in the latter pathological entity. It is suggested that these vasculopathies may represent different steps of the same lesion. On the other hand, they may also be the expression of a maternal immunological attack on placental tissues causing a deficit of placentation, low birthweight being the consequence of this deficit.

Immunohistochemical findings in acute atherosis associated with intrauterine growth retardation.

Lesions of acute atherosis in 23 placentas from pregnancies complicated by fetal growth retardation (less than tenth percentile) were studied by an immunoperoxidase staining. Twelve of them were from normotensive pregnancies, ten complicated by pregnancy induced hypertension, and the remaining associated with systemic lupus erythematosus. Twenty-three placentas with physiological changes of the spiral arteries corresponding to normal pregnancies served as controls. Six of the cases complicated by fetal growth retardation showed absence of physiological changes in basal decidua. Massive intramural granular deposits of IgM, a smaller amount of C3 and C1q, and slight deposits of IgA and IgG were found in vessels with acute atherosis. No intramural deposition of immunoglobulins or complement was observed in vessels with or without physiological changes. The presence of granular deposits of immunoglobulins and complement within the vessel walls with acute atherosis may be related to an immunological disorder, probably mediated by immune complexes.

Maternal Vascular Lesions in Pre-eclampsia and Intrauterine Growth Retardation

Placental bed biopsies were performed during caesarean section in a series of 137 patients. Analysis of the morphological findings confirms that vascular physiological changes were reduced in pre-eclampsia and in normotensive intrauterine growth retardation. In pre-eclampsia, acute atherosis in the decidual segments of uteroplacental arteries was a prominent feature. Intimal thickenings of the myometrial segments of the uteromaternal arteries were also noted. Normotensive intrauterine growth retardation cases were characterized by intimal thickenings of the myometrial segments of the uteroplacental arteries. Immunofluorescent investigations have demonstrated that the deep vascular stenoses were not associated with immunoglobulin deposition while in distal arterial segments displaying acute atherosis a positive immunofluorescence for IgG and fibrin and, more irregularly, for C'3 and IgM could be noted. These findings lead us to suggest that an immunological mechanism may be involved in the pathogenesis of acute atherosis.

7 - Epidemiology and Aetiology of the Growth Retarded Baby

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.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.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.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.

Vascular changes of endometrium in early pregnancy.

Spiral arteries, from curetted endometrium, of first-trimester pregnancies, were examined in 342 consecutive cases, comprising 150 primigravida and 192 multigravida . Vascular changes, similar to the "acute atherosis ," described at the end of pregnancy in preeclamptic women, were found. Primigravida had a statistically higher incidence of vascular changes than multigravida . The light microscopic changes were those of intimal proliferation with the presence of foam cells. These intimal cells were mostly myofibroblasts. Mucopolysaccharides also were found in the intima by both light microscopy and ultrastructural studies. The possible importance of the finding of vascular changes in spiral arteries in early pregnancy is discussed.

Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss, and a lupus anticoagulant

Evidence exists of an association between the presence of a "lupus" anticoagulant in plasma, recurrent fetal loss, and repeated thromboembolic accidents, also in the absence of systemic lupus erythematosus. Presented is an example of this association, with morphologic and biologic studies to elucidate its pathogenesis. In the case reported, the placenta showed massive infarction. In the spiral arteries of the basal plate of the placenta, lesions of intimal thickening, fibrinoid necrosis, acute atherosis, and intraluminal thrombosis were observed. The plasma of the patient contained a lupus anticoagulant and inhibited the formation of prostacyclin by rat aortic rings. Vascular production of prostacyclin is a major natural defense mechanism against thrombosis. Lack of generation of prostacyclin may account for the decidual vasculopathy and consequent placental infarction and for the generalized thrombotic tendency of some patients with lupus anticoagulant.

Fetal growth retardation and the maternal arterial supply of the human placenta in the absence of sustained hypertension.

In five patients with fetal growth retardation in pregnancies with no or only a moderate and transient rise in blood pressure, vascular lesions in the placental bed spiral arteries were found. These lesions are characterized by less well developed physiological morphological changes, by extensive intimal thickening, by fibrinoid degeneration of the media and by acute atherosis. the recurrent fetal growth retardation in these pregnancies may be the first clinical manifestation of underlying reno-vascular disease.

FETAL GROWTH RETARDATION AND THE ARTERIES OF THE PLACENTAL BED

summary The morphology of the placental bed spiral arteries was studied in 68 pregnancies complicated by fetal growth retardation and in 40 pregnancies with a normally grown fetus. When the birth weight was normal the extent and depth of physiological vascular changes were normal except in those pregnancies complicated by preeclampsia. When the birth weight was low and the mothers were normotensive the extent and depth of physiological vascular changes were either normal or restricted, and in all patients with hypertension and a baby with low birth weight the physiological changes were restricted to the decidual segments of the spiral (uteroplacental) arteries. Acute atherosis was only found in pregnancies complicated by hypertension, particularly if there was proteinuria. We do not believe that there exists an arteriopathy which is common to hypertensive and normotensive pregnancies complicated by fetal growth retardation.

Fetal growth retardation and the arteries of the placental bed.

The morphology of the placental bed spiral arteries was studied in 68 pregnancies complicated by fetal growth retardation and in 40 pregnancies with a normally grown fetus. When the birth weight was normal the extent and depth of physiological vascular changes were normal except in those pregnancies complicated by pre-eclampsia. When the birth weight was low and the mothers were normotensive the extent and depth of physiological vascular changes were either normal or restricted, and in all patients with hypertension and a baby with low birth weight the physiological changes were restricted to the decidual segments of the spiral (uteroplacental) arteries. Acute atherosis was only found in pregnancies complicated by hypertension, particularly if there was proteinuria. We do not believe that there exists an arteriopathy which is common to hypertensive and normotensive pregnancies complicated by fetal growth retardation.

The ultrastructure of acute atherosis in hypertensive pregnancy

Acute atherosis of the myometrial segments of the uteroplacental arteries from pre-eclamptic pregnancies was studied by electron microscopy. The lesions in their early stages are characterized by endothelial damage, insudation of plasma constituents into the vessel wall, proliferation of myointimal cells, and medial necrosis. Fat acculumation is seen first in myointimal cells and, later, macrophages engulf the lipid-rich debris released from disintegrating myogenic foam cells. Gross endothelial damage, massive intramural fibrin deposition, luminal thrombosis, and vessel rupture with hemorrhage are epiphenomena.

Beitrag zur Morphologie der myometrialen und dezidualen Arterien bei normalen Schwangerschaften, EPH-Gestosen und mütterlichem Diabetes mellitus

127 specimens, obtained by different methods from the myometrium and the placental bed after parturition, are investigated histologically. This material includes normal pregnancies as well as cases of maternal diabetes with and without hypertension and cases of hypertension in EPH-gestosis. The different parts of the arterial system (spiral arteries, basal arteries, radial arteries) are separately investigated. Physiologically, the pregnancy induces changes in the wall of the decidual arteries and possibly in the distal part of the radial arteries. The fibromuscular layer including the elastic fibers were destructed and replaced by fibrin and connective tissue. For this reason, in these parts of arteries it is very difficult to separate pathological from physiological changes. Maternal hypertension produces in myometrial, basal and decidual arteries (myometrial part) a thickening of the arterial wall. This thickening is caused in arteries with normal structure by hypertrophy of the media, in the spiral arteries by intimal processes (edematous reaction of the intima, deposition of foam cells) and fibrinoid necrosis of the arterial wall. The cases of maternal diabetes without hypertension are characterized by an increase of fibrin deposits in the wall of the distal part of the spiral artery. In the proximal part of the spiral artery we have found in two cases without hypertension some foam cells in the wall. Myometrial arteries show particularly thickening of the wall and narrowing of the arterial lumen, less frequently intimal swelling and groups of foam cells. In diabetes mellitus, complicated by hypertension, we could find changes in the proximal part of the spiral artery and in the basal arteries. This alterations correspond with the changes in cases of hypertension without diabetes. In the myometrial arteries the pathological processes are the same as in cases of diabetes without hypertension. A significant increase of pathological processes by the diabetes mellitus alone exists only in the myometrial arteries. Besides, in the small arterial vessels of the myometrium in diabetes occurs a proliferative angiolopathy, involving cases of White classes D and F only. We could demonstrate the so-called ‘acute atherosis’ in a small number of cases in the myometrial part of the spiral artery and in the distal part of the radial artery, too. It concerns especially cases of maternal hypertension, more seldom cases of normal pregnancy and diabetic pregnancy without hypertension.