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  1. AU="Opichka, Megan A"
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  1. Artikel ; Online: Vascular Dysfunction in Preeclampsia.

    Opichka, Megan A / Rappelt, Matthew W / Gutterman, David D / Grobe, Justin L / McIntosh, Jennifer J

    Cells

    2021  Band 10, Heft 11

    Abstract: Preeclampsia is a life-threatening pregnancy-associated cardiovascular disorder characterized by hypertension and proteinuria at 20 weeks of gestation. Though its exact underlying cause is not precisely defined and likely heterogenous, a plethora of ... ...

    Abstract Preeclampsia is a life-threatening pregnancy-associated cardiovascular disorder characterized by hypertension and proteinuria at 20 weeks of gestation. Though its exact underlying cause is not precisely defined and likely heterogenous, a plethora of research indicates that in some women with preeclampsia, both maternal and placental vascular dysfunction plays a role in the pathogenesis and can persist into the postpartum period. Potential abnormalities include impaired placentation, incomplete spiral artery remodeling, and endothelial damage, which are further propagated by immune factors, mitochondrial stress, and an imbalance of pro- and antiangiogenic substances. While the field has progressed, current gaps in knowledge include detailed initial molecular mechanisms and effective treatment options. Newfound evidence indicates that vasopressin is an early mediator and biomarker of the disorder, and promising future therapeutic avenues include mitigating mitochondrial dysfunction, excess oxidative stress, and the resulting inflammatory state. In this review, we provide a detailed overview of vascular defects present during preeclampsia and connect well-established notions to newer discoveries at the molecular, cellular, and whole-organism levels.
    Mesh-Begriff(e) Animals ; Blood Vessels/pathology ; Blood Vessels/physiopathology ; DNA, Mitochondrial/metabolism ; Endothelium, Vascular/pathology ; Endothelium, Vascular/physiopathology ; Female ; Humans ; Oxidative Stress ; Pre-Eclampsia/pathology ; Pre-Eclampsia/physiopathology ; Pregnancy ; Toll-Like Receptor 9/metabolism
    Chemische Substanzen DNA, Mitochondrial ; Toll-Like Receptor 9
    Sprache Englisch
    Erscheinungsdatum 2021-11-06
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10113055
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Mitochondrial-targeted antioxidant attenuates preeclampsia-like phenotypes induced by syncytiotrophoblast-specific Gαq signaling.

    Opichka, Megan A / Livergood, M Christine / Balapattabi, Kirthikaa / Ritter, McKenzie L / Brozoski, Daniel T / Wackman, Kelsey K / Lu, Ko-Ting / Kozak, Kaleigh N / Wells, Clive / Fogo, Agnes B / Gibson-Corley, Katherine N / Kwitek, Anne E / Sigmund, Curt D / McIntosh, Jennifer J / Grobe, Justin L

    Science advances

    2023  Band 9, Heft 48, Seite(n) eadg8118

    Abstract: Syncytiotrophoblast stress is theorized to drive development of preeclampsia, but its molecular causes and consequences remain largely undefined. Multiple hormones implicated in preeclampsia signal via the Gαq cascade, leading to the hypothesis that ... ...

    Abstract Syncytiotrophoblast stress is theorized to drive development of preeclampsia, but its molecular causes and consequences remain largely undefined. Multiple hormones implicated in preeclampsia signal via the Gαq cascade, leading to the hypothesis that excess Gαq signaling within the syncytiotrophoblast may contribute. First, we present data supporting increased Gαq signaling and antioxidant responses within villous and syncytiotrophoblast samples of human preeclamptic placenta. Second, Gαq was activated in mouse placenta using Cre-lox and DREADD methodologies. Syncytiotrophoblast-restricted Gαq activation caused hypertension, kidney damage, proteinuria, elevated circulating proinflammatory factors, decreased placental vascularization, diminished spiral artery diameter, and augmented responses to mitochondrial-derived superoxide. Administration of the mitochondrial-targeted antioxidant Mitoquinone attenuated maternal proteinuria, lowered circulating inflammatory and anti-angiogenic mediators, and maintained placental vascularization. These data demonstrate a causal relationship between syncytiotrophoblast stress and the development of preeclampsia and identify elevated Gαq signaling and mitochondrial reactive oxygen species as a cause of this stress.
    Mesh-Begriff(e) Animals ; Mice ; Pregnancy ; Female ; Humans ; Pre-Eclampsia ; Trophoblasts ; Placenta ; Antioxidants/pharmacology ; GTP-Binding Proteins ; Proteinuria
    Chemische Substanzen Antioxidants ; GTP-Binding Proteins (EC 3.6.1.-)
    Sprache Englisch
    Erscheinungsdatum 2023-12-01
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adg8118
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Krüppel-like factor 4 in transcriptional control of the three unique isoforms of Agouti-related peptide in mice.

    Ritter, McKenzie L / Wagner, Valerie A / Balapattabi, Kirthikaa / Opichka, Megan A / Lu, Ko-Ting / Wackman, Kelsey K / Reho, John J / Keen, Henry L / Kwitek, Anne E / Morselli, Lisa L / Geurts, Aron M / Sigmund, Curt D / Grobe, Justin L

    Physiological genomics

    2023  Band 56, Heft 3, Seite(n) 265–275

    Abstract: Agouti-related peptide (AgRP/ ...

    Abstract Agouti-related peptide (AgRP/
    Mesh-Begriff(e) Mice ; Animals ; Agouti-Related Protein/genetics ; Agouti-Related Protein/metabolism ; Kruppel-Like Factor 4 ; Neurons/metabolism ; Obesity/genetics ; Obesity/metabolism ; Hypothalamus/metabolism ; Protein Isoforms/genetics ; Protein Isoforms/metabolism
    Chemische Substanzen Agouti-Related Protein ; Kruppel-Like Factor 4 ; Protein Isoforms
    Sprache Englisch
    Erscheinungsdatum 2023-12-25
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2038823-8
    ISSN 1531-2267 ; 1094-8341
    ISSN (online) 1531-2267
    ISSN 1094-8341
    DOI 10.1152/physiolgenomics.00042.2023
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Angiotensin AT

    Balapattabi, Kirthikaa / Yavuz, Yavuz / Jiang, Jingwei / Deng, Guorui / Mathieu, Natalia M / Ritter, McKenzie L / Opichka, Megan A / Reho, John J / McCorvy, John D / Nakagawa, Pablo / Morselli, Lisa L / Mouradian, Gary C / Atasoy, Deniz / Cui, Huxing / Hodges, Matthew R / Sigmund, Curt D / Grobe, Justin L

    Cell reports

    2023  Band 42, Heft 8, Seite(n) 112935

    Abstract: Resting metabolic rate (RMR) adaptation occurs during obesity and is hypothesized to contribute to failed weight management. Angiotensin II (Ang-II) type 1 ( ... ...

    Abstract Resting metabolic rate (RMR) adaptation occurs during obesity and is hypothesized to contribute to failed weight management. Angiotensin II (Ang-II) type 1 (AT
    Mesh-Begriff(e) Animals ; Mice ; Agouti-Related Protein/metabolism ; Angiotensin II/metabolism ; Neurons/metabolism ; Obesity/metabolism ; Receptor, Angiotensin, Type 1/metabolism
    Chemische Substanzen Agouti-Related Protein ; Angiotensin II (11128-99-7) ; Agtr1a protein, mouse ; Receptor, Angiotensin, Type 1
    Sprache Englisch
    Erscheinungsdatum 2023-08-02
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112935
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Chronic intracerebroventricular infusion of angiotensin II causes dose- and sex-dependent effects on intake behaviors and energy homeostasis in C57BL/6J mice.

    Oliveira, Vanessa / Reho, John J / Balapattabi, Kirthikaa / Ritter, McKenzie L / Mathieu, Natalia M / Opichka, Megan A / Lu, Ko-Ting / Grobe, Connie C / Silva, Sebastião D / Wackman, Kelsey K / Nakagawa, Pablo / Segar, Jeffrey L / Sigmund, Curt D / Grobe, Justin L

    American journal of physiology. Regulatory, integrative and comparative physiology

    2022  Band 323, Heft 4, Seite(n) R410–R421

    Abstract: The renin-angiotensin system (RAS) within the brain is implicated in the control of fluid and electrolyte balance, autonomic functions, blood pressure, and energy expenditure. Mouse models are increasingly used to explore these mechanisms; however, sex ... ...

    Abstract The renin-angiotensin system (RAS) within the brain is implicated in the control of fluid and electrolyte balance, autonomic functions, blood pressure, and energy expenditure. Mouse models are increasingly used to explore these mechanisms; however, sex and dose dependencies of effects elicited by chronic intracerebroventricular (ICV) angiotensin II (ANG II) infusion have not been carefully established in this species. To examine the interactions among sex, body mass, and ICV ANG II on ingestive behaviors and energy balance, young adult C57BL/6J mice of both sexes were studied in a multiplexed metabolic phenotyping system (Promethion) during chronic infusion of ANG II (0, 5, 20, or 50 ng/h). At these infusion rates, ANG II caused accelerating dose-dependent increases in drinking and total energy expenditure in male mice, but female mice exhibited a complex biphasic response with maximum responses at 5 ng/h. Body mass differences did not account for sex-dependent differences in drinking behavior or total energy expenditure. In contrast, resting metabolic rate was similarly increased by ICV ANG II in a dose-dependent manner in both sexes after correction for body mass. We conclude that chronic ICV ANG II stimulates water intake, resting, and total energy expenditure in male C57BL/6J mice following straightforward accelerating dose-dependent kinetics, but female C57BL/6J mice exhibit complex biphasic responses to ICV ANG II. Furthermore, control of resting metabolic rate by ANG II is dissociable from mechanisms controlling fluid intake and total energy expenditure. Future studies of the sex dependency of ANG II within the brain of mice must be designed to carefully consider the biphasic responses that occur in females.
    Mesh-Begriff(e) Angiotensin II/pharmacology ; Animals ; Blood Pressure/physiology ; Female ; Homeostasis ; Infusions, Intraventricular ; Injections, Intraventricular ; Male ; Mice ; Mice, Inbred C57BL
    Chemische Substanzen Angiotensin II (11128-99-7)
    Sprache Englisch
    Erscheinungsdatum 2022-07-11
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 603839-6
    ISSN 1522-1490 ; 0363-6119
    ISSN (online) 1522-1490
    ISSN 0363-6119
    DOI 10.1152/ajpregu.00091.2022
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Uc I Zs.89: Hefte anzeigen Standort:
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  6. Artikel ; Online: Cardiometabolic Consequences of Deleting the Regulator of G protein Signaling-2 (

    Ritter, McKenzie L / Deng, Guorui / Reho, John J / Deng, Yue / Sapouckey, Sarah A / Opichka, Megan A / Balapattabi, Kirthikaa / Wackman, Kelsey K / Brozoski, Daniel T / Lu, Ko-Ting / Paradee, William J / Gibson-Corley, Katherine N / Cui, Huxing / Nakagawa, Pablo / Morselli, Lisa L / Sigmund, Curt D / Grobe, Justin L

    Hypertension (Dallas, Tex. : 1979)

    2022  Band 79, Heft 12, Seite(n) 2843–2853

    Abstract: Background: RGS (regulator of G protein signaling) family members catalyze the termination of G protein signaling cascades. Single nucleotide polymorphisms in the : Methods: To study cell-specific functions of RGS2, a novel gene-targeted mouse ... ...

    Abstract Background: RGS (regulator of G protein signaling) family members catalyze the termination of G protein signaling cascades. Single nucleotide polymorphisms in the
    Methods: To study cell-specific functions of RGS2, a novel gene-targeted mouse harboring a conditional allele for the
    Results: Whereas
    Conclusions: These results demonstrate the development of a novel mouse with conditional expression of
    Mesh-Begriff(e) Animals ; Mice ; Agouti-Related Protein ; Hypertension/genetics ; Mice, Knockout ; Mice, Transgenic ; Receptor, Angiotensin, Type 1/genetics ; Recombinases ; RGS Proteins/genetics
    Chemische Substanzen Agouti-Related Protein ; Receptor, Angiotensin, Type 1 ; Recombinases ; RGS Proteins
    Sprache Englisch
    Erscheinungsdatum 2022-10-19
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.122.20169
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 1488: Hefte anzeigen Standort:
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