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  • Ovid Technologies (Wolters Kluwer Health)  (14)
  • Dechend, Ralf  (14)
  • 1
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    Vitronectin Concentrations Predict Risk in Patients Undergoing Coronary Stenting
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Circulation: Cardiovascular Interventions Vol. 2, No. 1 ( 2009-02), p. 14-19
    Details
    In: Circulation: Cardiovascular Interventions, Ovid Technologies (Wolters Kluwer Health), Vol. 2, No. 1 ( 2009-02), p. 14-19
    Abstract: Background— Vitronectin is a multifunctional protein with a multiple binding domain that interacts with a variety of plasma and cell proteins. Vitronectin binds multiple ligands, including the soluble vitronectin receptor. Abciximab binds equally well to soluble vitronectin receptor and glycoprotein IIb/IIIa, because both share the β 3 subunit. We tested whether vitronectin concentrations correlate with adverse outcomes in acute coronary syndrome patients. Methods and Results— Baseline serum samples (n=233) from a randomized, placebo-controlled trial of abciximab plus stenting (Evaluation of Platelet IIb/IIIa Inhibitor for Stenting EPISTENT) were retrospectively analyzed. We stratified vitronectin concentrations into the 3 lower quartiles (n=178; 〈 49.7 μg/mL) versus the fourth upper quartile (n=55; ≥49.7 μg/mL). The end point was a major adverse cardiovascular event defined as death, myocardial infarction or urgent revascularization at 30 days and 6 months. A higher proportion of patients with baseline vitronectin ≥49.7 μg/mL had major adverse cardiovascular event than patients with baseline vitronectin 〈 49.7 μg/mL at 30 days (18.2% versus 5.6%; P =0.01) and 6 months (20.0% versus 6.2%; P =0.006). When baseline variables not predictive of major adverse cardiovascular event (eg, troponin positive, history of congestive heart failure, diabetes, history of hypertension, smoking status) were excluded from the multivariate model, only baseline vitronectin ≥49.7 μg/mL (at 30 days: OR, 3.23; 95% CI, 1.23, 8.49; at 6 months: OR, 3.36; 95% CI, 1.33, 8.52) and history of myocardial infarction (at 30 days: OR, 5.02; 95% CI, 1.41, 17.9; at 6 months: OR, 3.99; 95% CI, 1.28, 12.43) remained. No interaction occurred between abciximab and vitronectin. Conclusions— Our findings indicate that vitronectin may be an independent predictor of adverse cardiovascular outcomes following acute stenting.
    Type of Medium: Online Resource
    ISSN: 1941-7640 , 1941-7632
    URL: Article
    DOI: 10.1161/CIRCINTERVENTIONS.108.795799
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
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  • 2
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    Cardiovascular Biomarker Midregional Proatrial Natriuretic Peptide During and After Preeclamptic Pregnancies
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Hypertension Vol. 59, No. 2 ( 2012-02), p. 395-401
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 59, No. 2 ( 2012-02), p. 395-401
    Abstract: Preeclampsia is associated with increased risk of cardiovascular disease. Midregional proatrial natriuretic peptide (MR-proANP), a precursor of the atrial natriuretic peptide, is a biomarker for cardiovascular disease. We obtained plasma from 184 pregnant women in gestational weeks 24 to 42 (normotensive pregnancies: n=77, preeclampsia: n=107), from 25 of these women at 5 to 8 years after index pregnancy (normotensive pregnancies: n=11, preeclampsia: n=14), and from 49 normotensive, nonpregnant women and analyzed them by immunoassay for MR-proANP. To investigate potential sources, placental and decidual atrial natriuretic peptide mRNA expression levels were analyzed by quantitative real-time PCR in 21 normotensive and 23 preeclamptic pregnancies, as well as in human heart and kidney samples. For further confirmation, we measured circulating MR-proANP and performed expression studies in a transgenic rat model for preeclampsia. MR-proANP was significantly elevated in maternal plasma in preeclampsia compared with normotensive pregnancies (135 versus 56 pmol/L; P 〈 0.001). However, 5 to 8 years after pregnancy, there was no difference (formerly preeclamptic women versus formerly normotensive in pregnancy: 53 versus 49 pmol/L; P =0.5). Our preeclamptic rat model confirmed the acute MR-proANP differences between preeclamptic and normotensive pregnancies (10.9±1.9 versus 4.3±0.3 pmol/L; P =0.05). Atrial natriuretic peptide expression was high in the heart but negligible in the uteroplacental unit in both normotensive humans and rats, whereas expression in maternal and fetal hearts in the preeclamptic rats was significantly increased, compared with controls. MR-proANP is a serviceable biomarker in preeclampsia, both in humans and a rat model, probably reflecting cardiovascular hemodynamic stress.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.111.185264
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
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  • 3
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    Abstract 042: Cd74-dysregulation of Macrophage-trophoblastic Interactions in the Preeclamptic Placenta
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Hypertension Vol. 66, No. suppl_1 ( 2015-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 66, No. suppl_1 ( 2015-09)
    Abstract: Objectives: Preeclamptic pregnancies feature placental anomalies. Villous trophoblast differentiation during placental development is regulated by feto-placental macrophages and disturbance of this well-balanced regulation can lead to pathological pregnancies. We hypothesized that Cluster of differentiation 74 (CD74) dysregulation of placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia. Methods and Results: We performed microarray analysis of placental tissue. CD74 was one of the most down-regulated (-2.5 fold) genes in placentas from preeclamptic women. We confirmed this finding in early onset ( 〈 34 gestational week, n=26) and late onset (≥34 gestational week, n=24) samples from preeclamptic women, compared to healthy pregnant controls (n=28) by real-time RT-PCR and on protein level by Western blot and flow cytometry. We localized CD74 expression in placental macrophages by immunofluorescence, flow cytometry, and real-time RT-PCR. Number and mean fluorescence intensity (MFI) of CD74-positive macrophages were significantly lower in preeclamptic placentas (7692 MFI ± 4402), as compared to controls (16283 MFI ± 3047). In CD74-silenced macrophages, expression of adhesion molecules ALCAM (-2 fold), ICAM4 (-2.1 fold), and Syndecan-2 (-1.9 fold) was lower compared to control. Macrophage adhesion to a trophoblast layer were diminished (-1.3 fold). Naïve and activated macrophages lacking CD74 showed a shift towards a pro-inflammatory signature with an increased secretion of TNFalpha(21.8 pg/ml ± 13.2 vs. 8 pg/ml ± 4.3), CCL5 (1.9 ng/ml ± 0.4 vs. 0.8 ng/ml ± 0.2) and MCP-1 (3 ng/ml ± 2.6 vs. 1 ng/ml ± 0.5), when co-cultured with trophoblasts compared to control macrophages. CD74-knockout mice showed disturbed placental morphology, reduced junctional zone (1.6 mm2 ± 0.3 vs. 2.3 mm2 ± 0.5) and smaller placentas (0.09 g ± 0.01 vs. 0.11 g ± 0.02) with fetal growth restriction (0.7 g ± 0.1 vs. 0.9 g ± 0.2) when compared to WT mice. Conclusions: We found that CD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation led to altered macrophage activation towards a pro-inflammatory signature, a disturbed crosstalk with trophoblasts and an abnormal placental morphology.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.66.suppl_1.042
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
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  • 4
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    Heparin Strongly Induces Soluble Fms-Like Tyrosine Kinase 1 Release In Vivo and In Vitro—Brief Report
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 31, No. 12 ( 2011-12), p. 2972-2974
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 31, No. 12 ( 2011-12), p. 2972-2974
    Abstract: Soluble fms-like tyrosine kinase 1 (sFlt1) is involved in the pathophysiology of preeclampsia and coronary artery disease. Because sFlt1 has a heparin-binding site, we investigated whether or not heparin releases sFlt1 from the extracellular matrix. Methods and Results— We measured sFlt1 before and after heparin administration in 135 patients undergoing coronary angiography, percutanous coronary intervention, or both. sFlt1 was increased directly after heparin administration (from 254 to 13 440 pg/mL) and returned to baseline within 10 hours. Umbilical veins and endothelial cells treated with heparin released sFlt1. Heparinase I and III also increased sFlt1. Mice treated with heparin had elevated sFlt1 serum levels. Their serum inhibited endothelial tube formation. Conclusion— Heparin releases sFlt1 by displacing the sFlt1 heparin-binding site from heparan sulfate proteoglycans. Heparin could induce an antiangiogenic state.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.111.237784
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 1494427-3
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  • 5
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    Cytochrome P450 Subfamily 2J Polypeptide 2 Expression and Circulating Epoxyeicosatrienoic Metabolites in Preeclampsia
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Circulation Vol. 126, No. 25 ( 2012-12-18), p. 2990-2999
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 126, No. 25 ( 2012-12-18), p. 2990-2999
    Abstract: Preeclampsia is a multisystem disorder of pregnancy, originating in the placenta. Cytochrome P450 (CYP)-dependent eicosanoids regulate vascular function, inflammation, and angiogenesis, which are mechanistically important in preeclampsia. Methods and Results— We performed microarray screening of placenta and decidua (maternal placenta) from 25 preeclamptic women and 23 control subjects. The CYP subfamily 2J polypeptide 2 (CYP2J2) was upregulated in preeclamptic placenta and decidua. Reverse-transcription polymerase chain reaction confirmed the upregulation, and immunohistochemistry localized CYP2J2 in trophoblastic villi and deciduas at 12 weeks and term. The CYP2J2 metabolites, 5,6-epoxyeicosatrienoic acid (EET), 14,15-EET, and the corresponding dihydroxyeicosatrienoic acids, were elevated in preeclamptic women compared with controls in the latter two thirds of pregnancy and after delivery. Stimulating a trophoblast-derived cell line with the preeclampsia-associated cytokine tumor necrosis factor-α enhanced CYP2J2 gene and protein expression. In 2 independent rat models of preeclampsia, reduced uterine-perfusion rat and the transgenic angiotensin II rat, we observed elevated EET, dihydroxyeicosatrienoic acid, and preeclamptic features that were ameliorated by the CYP epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MsPPOH). Uterine arterial rings of these rats also dilated in response to MsPPOH. Furthermore, 5,6-EET could be metabolized to a thromboxane analog. In a bioassay, 5,6-EET increased the beating rate of neonatal cardiomyocytes. Blocking thromboxane synthesis reversed that finding and also normalized large-conductance calcium-activated potassium channel activity. Conclusions— Our data implicate CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the disturbed uteroplacental remodeling, leading to hypertension and endothelial dysfunction.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.112.127340
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
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  • 6
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    Hypertension in Response to Autoantibodies to the Angiotensin II Type I Receptor (AT1-AA) in Pregnant Rats : Role of Endothelin-1
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Hypertension Vol. 54, No. 4 ( 2009-10), p. 905-909
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 4 ( 2009-10), p. 905-909
    Abstract: Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) and endothelin -1 (ET-1) are suggested to be important links between placental ischemia and hypertension during preeclampsia. Activation of the angiotensin II type 1 receptor (AT1R) increases endothelial cell production of ET-1; however, the importance of ET-1 in response to AT1-AA–mediated AT1 R activation during preeclampsia is unknown. Furthermore, the role of AT1-AA–mediated increases in blood pressure during pregnancy remains unclear. The objective of this study was to test the hypothesis that AT1-AA, increased to levels observed in preeclamptic women and placental ischemic rats, increases mean arterial pressure (MAP) by activation of the ET-1 system. Chronic infusion of purified rat AT1-AA into normal pregnant (NP) rats for 7 days increased AT1-AA from 0.68±0.5 to 10.88±1.1 chronotropic units ( P 〈 0.001). The increased AT1-AA increased MAP from 99±1 to 119±2 mm Hg ( P 〈 0.001). The hypertension was associated with significant increases in renal cortices (11-fold) and placental (4-fold) ET-1. To determine whether ET-1 mediates AT1-AA–induced hypertension, pregnant rats infused with AT1-AA and NP rats were treated with an ET A receptor antagonist. MAP was 100±1 mm Hg in AT1-AA+ET A antagonist-treated rats versus 98±2 mm Hg in ET A antagonist-treated rats. Collectively, these data support the hypothesis that one potential pathway whereby AT1-AAs increase blood pressure during pregnancy is by an ET-1–dependent mechanism.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.109.137935
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
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  • 7
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    Novel Role for Inhibitor of Differentiation 2 in the Genesis of Angiotensin II–Induced Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2008
    In:  Circulation Vol. 117, No. 20 ( 2008-05-20), p. 2645-2656
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 117, No. 20 ( 2008-05-20), p. 2645-2656
    Abstract: Background— Angiotensin (Ang) II–induced target-organ damage involves innate and acquired immunity. Mice deficient for the helix-loop-helix transcription factor inhibitor of differentiation (Id2 −/− ) lack Langerhans and splenic CD8a+ dendritic cells, have reduced natural killer cells, and have altered CD8 T-cell memory. We tested the hypothesis that an alteration in the number and quality of circulating blood cells caused by Id2 deletion would ameliorate Ang II–induced target-organ damage. Methods and Results— We used gene-deleted and transgenic mice. We conducted kidney and bone marrow transplants. In contrast to Ang II–infused Id2 +/− , Id2 −/− mice infused with Ang II remained normotensive and failed to develop albuminuria or renal damage. Bone marrow transplant of Id2 +/− bone marrow to Id2 −/− mice did not restore the blunted blood pressure response to Ang II. Transplantation of Id2 −/− kidneys to Id2 +/− mice also could not prevent Ang II–induced hypertension and renal damage. We verified the Ang II resistance in Id2 −/− mice in a model of local tissue Ang II production by crossing hypertensive mice transgenic for rat angiotensinogen with Id2 −/− or Id2 +/− mice. Angiotensinogen-transgenic Id2 +/− mice developed hypertension, albuminuria, and renal injury, whereas angiotensinogen-transgenic Id2 −/− mice did not. We also found that vascular smooth muscle cells from Id2 −/− mice showed an antisenescence phenotype. Conclusions— Our bone marrow and kidney transplant experiments suggest that alterations in circulating immune cells or Id2 in the kidney are not responsible for Ang II resistance. The present studies identify a previously undefined role for Id2 in the pathogenesis of Ang II–induced hypertension.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.107.760116
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
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  • 8
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    Maternal Angiotensin Increases Placental Leptin in Early Gestation via an Alternative Renin-Angiotensin System Pathway : Suggesting a Link to Preeclampsia
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Hypertension Vol. 77, No. 5 ( 2021-05), p. 1723-1736
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 77, No. 5 ( 2021-05), p. 1723-1736
    Abstract: Various studies found an association of different renin-angiotensin system (RAS) components with gestational duration and preterm birth, as well as with preeclampsia. Approximately 25% of first-time pregnant women develop a mild to severe hypertension in pregnancy or even preeclampsia. Based on recently published single-cell RNA-sequencing, we hypothesized an alternative RAS function in placenta and furthermore, an implication in hypertensive disorders in pregnancy. Placental RAS expression and localization was analyzed via quantitative polymerase chain reaction and in situ mRNA padlock probes. Tissue was collected from first-trimester elective termination (n=198), from healthy third-trimester controls (n=54), from early-onset preeclamptic (n=54) and age-matched controls (n=29), as well as first-trimester placentae from women with a high uterine artery resistance index (high-risk for preeclampsia, n=9) and controls (n=8). Serum levels of Ang (angiotensin) I to IV from women before and after conception were measured via mass spectrometry (n=10). Placental explants were cultured in 2.5% oxygen with Ang II, candesartan, and leptin. Seahorse XF96 MitoStress assays assessed trophoblast metabolism. Here, we show that maternal angiotensin acts on placental LNPEP (leucine aminopeptidase), that is, angiotensin IV-receptor and fetal angiotensin on placental AGTR1 (angiotensin II receptor type 1). Maternal circulating RAS shifts towards Ang IV in pregnancy. Ang IV decreases trophoblastic mitochondrial respiration and increases placental leptin via placental LNPEP. Lower placental LNPEP in preeclampsia and in first-trimester patients at high-risk for preeclampsia suggests a new alternative route in maternal RAS signaling and may contribute to hypertension and disease in pregnancy. The study shows how hypertensive disorders in pregnancy may be connected metabolic alterations that finally seem to contribute to the multifactorial disease in pregnancy, preeclampsia.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.120.16425
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 9
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    Abstract 542: Progesterone Supplementation Attenuates Hypertension And AT1-AA in Response Tt Elevated IL-6 During Pregnancy
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Hypertension Vol. 62, No. suppl_1 ( 2013-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 62, No. suppl_1 ( 2013-09)
    Abstract: Preeclampsia is a multi-system disorder defined as new-onset hypertension with proteinuria developing after 20 weeks gestation. Preeclampsia remains a significant contributor to maternal morbidity and mortality, with great impact in perinatal morbidity. Research efforts throughout the world have focused on alternative therapies for the treatment of preeclampsia to the mainstay treatment of delivery of the fetus and placenta. 17-alpha-hydroxyprogesterone caproate (17-OHP) is a synthetic metabolite of progesterone used effectively for the prevention of recurrent preterm birth in singleton pregnancies. Previously we identified potential role for 17-OHP as an anti-inflammatory that suppressed inflammatory cytokines, hypertension and endothelin-1 in response to placental ischemia in the RUPP rat model of preeclampsia. In the current study we examined a role 17-OHP to blunt the pathophysiological effects to elevated IL-6 during pregnancy. IL-6 induced hypertension during pregnancy occurs with increased renin activity, autoantibodies to the angiotensin II type I receptor (AT1-AA) and reduced kidney function. This experiment was performed in the following groups of normal pregnant rats: NP (n=5); NP+17-OHP (n=6); NP+IL-6 (n=10); NP+IL-6+17-OHP (n=10). To test our hypothesis IL-6 (5ng/day) was infused via miniosmotic pump into normal pregnant rats beginning on day 14 of gestation and 17-OHP (3.32mg/kg) was diluted in normal saline and injected on day 18. Blood pressure (MAP) determination and serum collection was performed on day 19 of gestation. MAP in NP was 100+3mmHg which increased with IL-6 to 112+4mmHg, p 〈 0.05. Pregnant rats given 17-OHP alone had a MAP of 99+3mmHg and MAP only increased to 103+2mmHg in IL-6+17-OHP. AT1-AA was 1.2+0.5 bpm in NP rats and increased to 17+9 bpm with IL-6 infusion. Administration of 17-OHP significantly blunted AT1-AA to 4+0.8bpm in NP+IL-6+17-OHP. Importantly, this study illustrates that 17-OHP attenuates hypertension and AT1-AA in response to elevated IL-6 during pregnancy and could lend hope to a new potential therapeutic for preeclampsia.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.62.suppl_1.A542
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
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  • 10
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    Abstract 27: Unravelling Cell-specific Interactions At The Preeclamptic Maternal-foetal Interface From Early To Late Pregnancy
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Hypertension Vol. 78, No. Suppl_1 ( 2021-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 78, No. Suppl_1 ( 2021-09)
    Abstract: Preeclamptic syndrome arrises in the fetal part of the placenta (villi). In this study, we analyse placental development by single nuclei RNA-sequencing in early and term pregnancy and draw conclusions about pathological processes in preeclampsia (PE) that originate early in gestation. We profiled the transcriptome of 101,067 nuclei obtained from a total of 12 pregnancies, spanning early, term and PE doners. Using unsupervised computational approaches, we identified 12 and 16 different cell types and states in decidua and villi, respectively. Our comprehensively identified catalogue of cell types and states aligns well with the previous single cell studies. We identified different subpopulations of syncytiotrophoblast and GATA3+/GREM2+ trophoblast stem cells (TSC) in villi. Through gestation, gene expression in cell populations from the matrisome or vascular environments show dynamic expression reflecting vascular development associated with spiral artery remodelling and concordant decidual stroma reorganisation. Global differential gene expression analysis shows that trophoblast cell types are most dysregulated in PE. Cell-cell communication analysis revealed important dysregulation between villi and decidual cell types. The secretory signalling characteristic of this trophoblastic disease may be used for early biomarker screening. Overall, this study paves the way to a deeper understanding of the early pathophysiology of PE. Figure 1: Villi (v) and decidua (d) cell clusters from early, late control and preeclampsia (PE) villi and decidua visualised as a UMAP. Datasets were integrated separately for each tissue and merged for embedding.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.78.suppl_1.27
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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