Effect of Smoking on Circulating Angiogenic Factors in High Risk Pregnancies

Objective: Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), and the pro-angiogenic placental growth factor (PlGF) precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng) in women at high risk for developing preeclampsia. Study Design: We performed a secondary analysis of serum samples from 993 high-risk women (chronic hypertension, diabetes, multifetal gestation, and previous preeclampsia) in a preeclampsia prevention trial. sFlt1, sEng and PlGF were measured in serum samples obtained at study entry, which was prior to initiation of aspirin (median 19.0 weeks' [interquartile range of 16.0-22.6 weeks']). Smoking status was determined by self-report. Results: sFlt1 was not significantly different in smokers from any high-risk groups compared to their nonsmoking counterparts. PlGF was higher among smokers compared to nonsmokers among diabetic women (142.7 [77.4-337.3] vs 95.9 [48.5-180.7] pg/ml, p = 0.005) and women with a history of preeclampsia (252.2 [137.1-486.0] vs 152.2 [73.6-253.7] pg/ml, p = 0.001). sEng was lower in smokers with multifetal gestations (5.8 [4.6-6.5] vs 6.8 [5.5-8.7] ng/ml, p = 0.002) and trended lower among smokers with diabetes (4.9 [3.8-5.6] vs 5.3 [4.3-6.3] ng/ml, p = 0.05). Smoking was not associated with a lower incidence of preeclampsia in any of these groups. Conclusions: In certain high-risk groups, smoking is associated with changes in the concentrations of these factors towards a pro-angiogenic direction during early pregnancy; however, there was no apparent association between smoking and the development of preeclampsia in our cohort

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Current debates on immunology of preeclampsia. Report of the sixth international workshop of Reunion Island (Indian Ocean, December 2008)

Les troubles hypertensifs de la grossesse (THG) représentent globalement 10 % des naissances humaines, et leur complication majeure, la prééclampsie, 3 à 5 %. L’étiologie de ces THG reste toujours controversée ; cependant des avancées majeures ont eu lieu ces dernieres 25 années. Le « sixième colloque international d’immunologie de la reproduction, de l’immunotolérance et de l’immunologie de la prééclampsie » 2008 a fêté cette année son dixième anniversaire. Durant cette décennie, ces six colloques bisannuels ont largement contribué à nourrir le débat entre immunologistes, cliniciens, anthropologues et spécialistes des maladies cardiovasculaires. Le défaut de l’invasion trophoblastique profonde obligatoire chez les humains rencontrée dans la prééclampsie, le retard de croissance intra-utérin, et dans une certaine mesure dans la menace d’accouchement prématuré n’ont été compris qu’à la fin des années 1970. Dans le même temps, des études cliniques et épidémiologiques à la fin du xxe siècle ont permis de réaliser que la prééclampsie « maladie des primipares » pouvait en fait être une maladie de la première grossesse au niveau d’un couple. Parmi les avancées significatives, l’immunologie de la reproduction a fait des bonds de géant dans la dernière décennie. Ce papier relate les étapes majeures franchies dans la compréhension de cette pathologie et met en lumière l’intérêt de ces travaux immunologiques et des nouveaux concepts afférents. Il semble, en ce début de xxie siècle que nous soyons plus près que jamais de comprendre l’étiologie de cette énigme obstétricale. Dans ce domaine, l’immunologie de la reproduction sera sans doute un des interlocuteurs majeurs.Hypertensive disorders of pregnancy (HDP) represent globally 10% of human births and their major complication, preeclampsia, 3 to 5%. The etiology of these HDP remains still uncertain, however major advances have been made these last 25 years. The Sixth International Workshop on Reproductive Immunology, Immunological Tolerance and Immunology of Preeclampsia 2008 celebrated its 10th Anniversary in Reunion-island (French overseas Department in the Indian Ocean). Over this decade, these six workshops have contributed extensively to immunological, epidemiological, anthropological and even vascular debates. The defect of trophoblastic invasion encountered in preeclampsia, intra-uterine growth retardation and to some extend also preterm labour has been understood only at the end of the 1970's. On the other hand, clinical and epidemiological findings at the end of the 20th century permitted to apprehend that “preeclampsia disease of primiparae” may in fact well be the disease of first pregnancies at the level of human couples. Among the important advances, immunology of reproduction is certainly the topic where knowledge has literally exploded in the last decade. This paper relates some major steps in comprehension of this disease and focuses on the interest to follow these immunological works and their new concepts. It seems, at the beginning of the 21st century, that we are possibly closer than ever to understand the etiology of this obstetrical enigma. In this quest, the immunology of reproduction will certainly come out as one of the main players