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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preeclampsia is a systemic syndrome of pregnancy that originates in the placenta and is characterized by widespread maternal endothelial dysfunction. Until recently, the molecular pathogenesis of preeclampsia was largely unknown, but recent work suggests a key role for altered expression of placental antiangiogenic factors. Soluble Flt1 and soluble endoglin, secreted by the placenta, are increased in the maternal circulation weeks before the onset of preeclampsia. These antiangiogenic factors produce systemic endothelial dysfunction, resulting in hypertension, proteinuria, and the other systemic manifestations of preeclampsia. The molecular basis for placental dysregulation of these pathogenic factors remains unknown, and the role of angiogenic proteins in early placental vascular development is just beginning to be explored. These discoveries have exciting clinical implications and are likely to transform the detection and treatment of preeclampsia in the future.
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PMID:Preeclampsia and angiogenic imbalance. 1793 87

The case history is presented of a male infant who was thought to have idiopathic pulmonary arterial hypertension (PAH) at 3 months of age. Subsequently the PAH decreased unexpectedly and diffuse pulmonary arteriovenous malformations (PAVMs) were seen at 6.9 years of age for the first time. Hereditary haemorrhagic telangiectasia type 1 (HHT1) related to an endoglin mutation was diagnosed. At 10.3 years of age a lung biopsy showed diffuse PAVMs as well as pulmonary arteriopathy with medial hypertrophy. This is the first case of HHT1 presenting with PAH at such a young age. The subsequent decrease in pulmonary arterial pressure (PAP) was probably caused by the development of PAVMs. In the presence of PAVMs, measurement of the PAP may underestimate the extent of PAH-related vasculopathy.
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PMID:Early-life pulmonary arterial hypertension with subsequent development of diffuse pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia type 1. 1815 74

Preeclampsia is a serious complication during pregnancy that includes potentially life-threatening risks to the mother and fetus. It may be challenging to distinguish this from other causes of rapidly escalating hypertension, especially in women with end-stage renal disease, because current diagnostic criteria for preeclampsia cannot be easily applied. We report a woman undergoing hemodialysis who was considered to be preeclamptic when her blood pressure suddenly increased during her 29th week of gestation. At that time, she underwent emergent cesarean section. The presence of a normal-sized placenta with no histological evidence of preeclampsia and retrospective analyses of maternal antiangiogenic biomarkers (soluble fms-like tyrosine kinase-1 and soluble endoglin) that were within normal levels for pregnancy suggest an alternative diagnosis. There is growing evidence that circulating levels of these proteins cause the preeclamptic phenotypes and also are sensitive and specific predictors and markers of this disease, suggesting that measurements of soluble fms-like tyrosine kinase-1 and soluble endoglin be considered in such difficult diagnostic dilemmas as the cause of hypertension in pregnant dialysis patients. Additional studies in this particular group of patients are required.
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PMID:Use of circulating antiangiogenic factors to differentiate other hypertensive disorders from preeclampsia in a pregnant woman on dialysis. 1845 53

Pre-eclampsia is a pregnancy-related condition characterized by hypertension, proteinuria and endothelial dysfunction. VEGF(165)b, formed by alternative splicing of VEGF (vascular endothelial growth factor) pre-mRNA, inhibits VEGF(165)-mediated vasodilation and angiogenesis, but has not been quantified in pregnancy. ELISAs were used to measure means+/-S.E.M. plasma VEGF(165)b, sEng (soluble endoglin) and sFlt-1 (soluble fms-like tyrosine kinase-1). At 12 weeks of gestation, the plasma VEGF(165)b concentration was significantly up-regulated in plasma from women who maintained normal blood pressure throughout their pregnancy (normotensive group, 4.90+/-1.6 ng/ml; P<0.01, as determined using a Mann-Whitney U test) compared with non-pregnant women (0.40+/-0.22 ng/ml). In contrast, in patients who later developed pre-eclampsia, VEGF(165)b levels were lower than in the normotensive group (0.467+/-0.209 ng/ml), but were no greater than non-pregnant women. At term, plasma VEGF(165)b concentrations were greater than normal in both pre-eclamptic (3.75+/-2.24 ng/ml) and normotensive (10.58 ng/ml+/-3.74 ng/ml; P>0.1 compared with pre-eclampsia) pregnancies. Patients with a lower than median plasma VEGF(165)b at 12 weeks had elevated sFlt-1 and sEng pre-delivery. Concentrations of sFlt-1 (1.20+/-0.07 and 1.27+/-0.18 ng/ml) and sEng (4.4+/-0.18 and 4.1+/-0.5 ng/ml) were similar at 12 weeks of gestation in the normotensive and pre-eclamptic groups respectively. Plasma VEGF(165)b levels were elevated in pregnancy, but this increase is delayed in women that subsequently develop pre-eclampsia. In conclusion, low VEGF(165)b may therefore be a clinically useful first trimester plasma marker for increased risk of pre-eclampsia.
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PMID:Failure to up-regulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia. 1907 60

Understanding the mechanisms of disease responsible for the syndrome of pre-eclampsia (PE) as well as early risk assessment is still a major challenge. Risk factors for PE are nulliparity, a family or own history of PE, pre-existing diabetes or increased body mass index, multiple pregnancy, maternal age, renal disease, hypertension or raised blood pressure at booking and chronic autoimmune disease. Other factors are thrombophilias and insulin resistance together with obesity. On the other hand identification of predictors of the development of pre-eclampsia would enhance the ability to diagnose women likely to develop pre-eclampsia before the onset of the disease and would improve their monitoring and enable to convey them to randomized trials for evaluating prophylactic treatment. A number of biochemical agents have been assessed as markers for predicting pre-eclampsia. None of them has been proved to be of clinical value yet. Much effort has been put into evaluating novel potential markers and their combination with other screening methods such as Doppler sonography. The most promising biochemical markers, to date, are placenta protein 13 (PP-13) as well as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). These markers allow screening at a relatively early stage and, most importantly, show relatively high predictive values and improved diagnostic performance if combined with first trimester Doppler sonography. However, until now, too little data are available to justify the clinical use of these markers. Large-scale prospective studies, assessing these markers, are important to advance progress in reducing maternal and perinatal morbidity and relieving the heavy burden of pre-eclampsia.
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PMID:Predictors and risk factors of pre-eclampsia. 1885 8

Senescence of endothelial cells (ECs) may contribute to age-associated cardiovascular diseases, including atherosclerosis and hypertension. The functional and gene expression changes associated with cellular senescence are poorly understood. Here, we have analyzed the expression, during EC senescence, of 2 different isoforms (L, long; S, short) of endoglin, an auxiliary transforming growth factor (TGF)-beta receptor involved in vascular remodeling and angiogenesis. As evidenced by RT-PCR, the S/L ratio of endoglin isoforms was increased during senescence of human ECs in vitro, as well as during aging of mice in vascularized tissues. Next, the effect of S-endoglin protein on the TGF-beta receptor complex was studied. As revealed by coimmunoprecipitation assays, S-endoglin was able to interact with both TGF-beta type I receptors, ALK5 and ALK1, although the interaction with ALK5 was stronger than with ALK1. S-endoglin conferred a lower proliferation rate to ECs and behaved differently from L-endoglin in relation to TGF-beta-responsive reporters with ALK1 or ALK5 specificities, mimicking the behavior of the endothelial senescence markers Id1 and plasminogen activator inhibitor-1. In situ hybridization studies demonstrated the expression of S-endoglin in the endothelium from human arteries. Transgenic mice overexpressing S-endoglin in ECs showed hypertension, decreased hypertensive response to NO inhibition, decreased vasodilatory response to TGF-beta(1) administration, and decreased endothelial nitric oxide synthase expression in lungs and kidneys, supporting the involvement of S-endoglin in the NO-dependent vascular homeostasis. Taken together, these results suggest that S-endoglin is induced during endothelial senescence and may contribute to age-dependent vascular pathology.
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PMID:S-endoglin expression is induced in senescent endothelial cells and contributes to vascular pathology. 1897 88

Arteriovenous malformations (AVMs) are direct connections between arteries and veins associated with loss of the intervening capillary bed. In the lungs, pulmonary AVMs can result in right to left shunts and severe cyanosis and dyspnoea. However, the cellular and molecular mechanisms underlying AVM formation are poorly understood. One important clue comes from the fact that pulmonary AVMs frequently occur in the familial disease hereditary haemorrhagic telangiectasia (HHT), which is associated with mutations in one of two receptors involved in transforming growth factor-beta family signalling, either endoglin (ENG) or activin receptor-like kinase 1 (ACVRL1, also known as ALK1). To elucidate the potential link between ENG or ACVRL1 deficiency and AVM formation in HHT, we performed a comprehensive study of Acvrl1 and Eng expression in wild-type and Eng-deficient (Eng+/-) mouse lungs using a combination of immunohistochemistry and RT-PCR from laser-microdissected arteries, veins and capillaries. We found that Eng and Acvrl1 have distinct expression profiles in the pulmonary vasculature and are only co-expressed in the distal (pre-capillary) arteries, distal veins and capillaries, consistent with the tendency for pulmonary AVMs to form in the distal pulmonary vessels in HHT. Downstream pSmad1/5/8 activity was found in the distal arteries and was specifically reduced in Eng+/- mice, consistent with previous in vitro data showing that Eng promotes Acvrl1-mediated Smad1/5/8 phosphorylation. Eng was more widely expressed than Acvrl1 in the lungs, as Eng alone was found in pulmonary veins, potentially explaining the increased frequency of AVMs in HHT1 patients. Furthermore, the association of ACVRL1 mutations with a second vascular disease, familial pulmonary artery hypertension, underlines the importance of ACVRL1 expression in the distal arteries that are affected in this disorder.
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PMID:Endoglin and activin receptor-like-kinase 1 are co-expressed in the distal vessels of the lung: implications for two familial vascular dysplasias, HHT and PAH. 1901 42

Pre-eclampsia, a pregnancy complication characterized by hypertension and proteinuria, is still a major cause of neonatal and maternal mortality, and acute and long-term morbidities for both mother and neonate. There is mounting evidence that an imbalance between angiogenic factors, such as VEGF (vascular endothelial growth factor) or PlGF (placental growth factor), and factors inhibiting angiogenesis, such as sFlt1 (soluble fms-like tyrosine kinase 1) and sEng (soluble endoglin), are closely related to the pathogenesis of pre-eclampsia. In the present issue of Clinical Science, Bills and co-workers report that VEGF(165)b, an alternative splice variant of the VEGF pre-mRNA, is up-regulated in women with normal pregnancy and that this increase was delayed or diminished in women who developed pre-eclampsia. Thus this protein could serve (alone or in combination with other parameters) as a new marker for risk assessment in terms of pre-eclampsia.
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PMID:Angiogenic factors and pre-eclampsia: an early marker is needed. 1882 76

Recent clinical studies indicate that an excess of angiostatic factors, such as soluble endoglin (sEng), is related to the occurrence of preeclampsia. Although recent clinical studies report that sEng is increased in preeclamptic women, the mechanisms underlying its overexpression remain unclear. Evidence suggests that hypoxia and induction of heme oxygenase-1 have opposing effects on sEng expression, the former stimulatory and the latter inhibitory. Hence, we hypothesized that placental ischemia because of reduced uterine perfusion pressure (RUPP) in the pregnant rat would increase sEng expression and decrease heme oxygenase-1. Mean arterial pressure was obtained via arterial catheter, and serum and placental proteins were measured by Western blot. Mean arterial pressure was increased (132+/-3 mm Hg versus 102+/-2 mm Hg; P<0.001), and fetal (2.35+/-0.05 g versus 1.76+/-0.08 g; P<0.001) and placental weight were decreased (0.47+/-0.04 g versus 0.58+/-0.03 g; P<0.01) in the RUPP compared with normal pregnant controls. Serum sEng (0.10+/-0.02 arbitrary pixel units [apu] versus 0.05+/-0.01 apu; P<0.05) and placental endoglin (4.7+/-2.3 apu versus 1.45+/-0.42 apu; P<0.05) were increased along with placental hypoxia inducible factor-1 alpha (1.42+/-0.25 apu versus 0.68+/-0.09 apu; P<0.05) expression in the RUPP versus the normal pregnant dams. Placental HO-1 (1.4+/-0.3 apu versus 2.5+/-0.1 apu; P<0.05) expression decreased in the RUPP compared with normal pregnant dams. The present findings support our hypothesis that placental ischemia because of RUPP increases the expression of sEng and shifts the balance of angiogenic factors in the maternal circulation toward an angiostatic state. The present study provides further evidence that placental ischemia is a strong in vivo stimulus of angiostatic factors during pregnancy.
Hypertension 2009 Feb
PMID:Hypertension produced by placental ischemia in pregnant rats is associated with increased soluble endoglin expression. 1907 97

Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, resolves on delivery of the placenta. Normal pregnancy is itself characterized by systemic inflammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. This is exacerbated in preeclampsia with an associated breakdown of compensatory mechanisms, eventually leading to placental and vascular dysfunction. The underlying pathology of preeclampsia is thought to be a relatively hypoxic or ischemic placenta. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can interact to produce peroxynitrite a powerful prooxidant that covalently modifies proteins by nitration of tyrosine residues, to possibly alter vascular function in preeclampsia. The linkage between placental hypoxia and maternal vascular dysfunction has been proposed to be via placental syncytiotrophoblast basement membranes shed by the placenta or via angiogenic factors which include soluble flt1 and endoglin secreted by the placenta that bind vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) in the maternal circulation. There is also abundant evidence of altered reactivity of the maternal and placental vasculature and of the altered production of autocoids in preeclampsia. The occurrence of preeclampsia is increased in women with preexisting vascular disease and confers a long-term risk for development of cardiovascular disease. The vascular stress test of pregnancy thus identifies those women with a previously unrecognized at risk vascular system and promotes the development of preeclampsia. Preexisting maternal vascular dysfunction intensified by placental factors is possibly responsible for the individual pathologies of preeclampsia.
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PMID:Vascular biology of preeclampsia. 1908 23


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