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  1. Article ; Online: Unraveling the role of resistin, retinol-binding protein 4 and adiponectin produced by epicardial adipose tissue in cardiac structure and function: evidence of a paracrine effect.

    Christou, Georgios A / Andriopoulou, Christina E / Liakopoulou, Alexandra / Tsape, Eirini / Apostolakis, Efstratios / Tselepis, Alexandros D / Konstandi, Maria / Frühbeck, Gema / Kiortsis, Dimitrios N

    Hormones (Athens, Greece)

    2023  Volume 22, Issue 2, Page(s) 321–330

    Abstract: Purpose: Adipokines produced by adipose tissue have been found to be involved in the pathophysiology of metabolic and cardiovascular diseases. We aimed to investigate the relationships of resistin, retinol-binding protein 4 (RBP4) and adiponectin ... ...

    Abstract Purpose: Adipokines produced by adipose tissue have been found to be involved in the pathophysiology of metabolic and cardiovascular diseases. We aimed to investigate the relationships of resistin, retinol-binding protein 4 (RBP4) and adiponectin produced by epicardial adipose tissue with coronary artery disease (CAD) and cardiac structure and function.
    Methods: Forty-one non-diabetic males scheduled for cardiothoracic surgery were examined. Anthropometric measurements, echocardiography, coronary angiography, and blood analysis were performed preoperatively. We measured the serum levels of resistin, RBP4, and adiponectin and their mRNA expression in thoracic subcutaneous adipose tissue and two epicardial adipose tissue samples, one close to left anterior descending artery (LAD) (resistin-LAD, RBP4-LAD, adiponectin-LAD), and another close to the right coronary artery (RCA) (resistin-RCA, RBP4-RCA, adiponectin-RCA).
    Results: Left ventricular (LV) ejection fraction correlated negatively with adiponectin-LAD (rho =  - 0.390, p = 0.025). The ratio of early to late diastolic transmitral flow velocity, as an index of LV diastolic function, correlated negatively with resistin-LAD (rho =  - 0.529, p = 0.024) and RBP4-LAD (rho =  - 0.458, p = 0.049). There was no difference in epicardial adipose tissue mRNA expression of resistin, RBP4, and adiponectin between individuals with CAD and those without CAD. When we compared the individuals with CAD in the LAD with those without CAD in the LAD, there was no difference in resistin-LAD, RBP4-LAD, and adiponectin-LAD. There was no difference in resistin-RCA, RBP4-RCA, and adiponectin-RCA between the individuals with CAD in the RCA and those without CAD in the RCA.
    Conclusion: Elevation of epicardial adipose tissue mRNA expression of adiponectin was associated with LV systolic dysfunction, while that of both resistin and RBP4 was linked to LV diastolic dysfunction.
    MeSH term(s) Male ; Humans ; Adiponectin ; Resistin ; Adipose Tissue/metabolism ; Coronary Artery Disease ; RNA, Messenger/genetics ; Retinol-Binding Proteins/metabolism ; Retinol-Binding Proteins, Plasma/genetics ; Retinol-Binding Proteins, Plasma/metabolism
    Chemical Substances Adiponectin ; Resistin ; RNA, Messenger ; Retinol-Binding Proteins ; RBP4 protein, human ; Retinol-Binding Proteins, Plasma
    Language English
    Publishing date 2023-03-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2075912-5
    ISSN 2520-8721 ; 1109-3099
    ISSN (online) 2520-8721
    ISSN 1109-3099
    DOI 10.1007/s42000-023-00447-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Sex steroid hormones differentially regulate CYP2D in female wild-type and CYP2D6-humanized mice.

    Konstandi, Maria / Andriopoulou, Christina E / Cheng, Jie / Gonzalez, Frank J

    The Journal of endocrinology

    2020  Volume 245, Issue 2, Page(s) 301–314

    Abstract: The CYP2D subfamily catalyses the metabolism of about 25% of prescribed drugs, including the majority of antidepressants and antipsychotics. At present, the mechanism of hepatic CYP2D regulation remains largely unknown. This study investigated the role ... ...

    Abstract The CYP2D subfamily catalyses the metabolism of about 25% of prescribed drugs, including the majority of antidepressants and antipsychotics. At present, the mechanism of hepatic CYP2D regulation remains largely unknown. This study investigated the role of sex steroid hormones in CYP2D regulation. For this purpose, Cyp2d22 expression was assessed in the distinct phases of the estrous cycle of normocyclic C57BL/6J (WT) female mice. Cyp2d22 was also evaluated in ovariectomised WT and CYP2D6-humanized (hCYP2D6) mice that received hormonal supplementation with either 17β-estradiol (E2) and/or progesterone. Comparisons were also made to male mice. The data revealed that hepatic Cyp2d22 mRNA, protein and activity levels were higher at estrous compared to the other phases of the estrous cycle and that ovariectomy repressed Cyp2d22 expression in WT mice. Tamoxifen, an anti-estrogenic compound, also repressed hepatic Cyp2d22 via activation of GH/STAT5b and PI3k/AKT signaling pathways. Both hormones prevented the ovariectomy-mediated Cyp2d22 repression. In case of progesterone, this may be mediated by inhibition of the PI3k/AKT/FOX01 pathway. Notably, Cyp2d22 mRNA levels in WT males were similar to those in ovariectomised mice and were markedly lower compared to females at estrous, a differentiation potentially regulated by the GH/STAT5b pathway. Sex steroid hormone-related alterations in Cyp2d22 mRNA expression were highly correlated with Hnf1a mRNA. Interestingly, fluctuations in Cyp2d22 in hippocampus and cerebellum followed those in liver. In contrast to WT mice, ovariectomy induced hepatic CYP2D6 expression in hCYP2D6 mice, whereas E2 and/or progesterone prevented this induction. Apparently, sex steroid hormones display a significant gender- and species-specific role in the regulation of CYP2D.
    MeSH term(s) Animals ; Cytochrome P-450 CYP2D6/metabolism ; Cytochrome P450 Family 2/metabolism ; Estradiol/administration & dosage ; Estrous Cycle/metabolism ; Female ; Gene Expression Regulation/physiology ; Gonadal Steroid Hormones/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Ovariectomy ; Progesterone/administration & dosage ; RNA, Messenger/metabolism ; Signal Transduction/genetics
    Chemical Substances Gonadal Steroid Hormones ; RNA, Messenger ; Progesterone (4G7DS2Q64Y) ; Estradiol (4TI98Z838E) ; Cytochrome P-450 CYP2D6 (EC 1.14.14.1) ; Cytochrome P450 Family 2 (EC 1.14.14.1)
    Language English
    Publishing date 2020-02-27
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 3028-4
    ISSN 1479-6805 ; 0022-0795
    ISSN (online) 1479-6805
    ISSN 0022-0795
    DOI 10.1530/JOE-19-0561
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Oleuropein-Induced Acceleration of Cytochrome P450-Catalyzed Drug Metabolism: Central Role for Nuclear Receptor Peroxisome Proliferator-Activated Receptor α.

    Malliou, Foteini / Andriopoulou, Christina E / Gonzalez, Frank J / Kofinas, Aristeidis / Skaltsounis, Alexios-Leandros / Konstandi, Maria

    Drug metabolism and disposition: the biological fate of chemicals

    2021  Volume 49, Issue 9, Page(s) 833–843

    Abstract: Oleuropein (OLE), the main constituent ... ...

    Abstract Oleuropein (OLE), the main constituent of
    MeSH term(s) Animals ; Anti-Inflammatory Agents/pharmacokinetics ; Cardiotonic Agents/pharmacokinetics ; Cytochrome P-450 Enzyme System/classification ; Cytochrome P-450 Enzyme System/metabolism ; Drug Interactions ; Gene Expression Regulation ; Inactivation, Metabolic/drug effects ; Iridoid Glucosides/pharmacokinetics ; Mice ; Oleaceae ; PPAR alpha/metabolism ; Phytochemicals/pharmacokinetics ; Prescription Drugs/pharmacokinetics
    Chemical Substances Anti-Inflammatory Agents ; Cardiotonic Agents ; Iridoid Glucosides ; PPAR alpha ; Phytochemicals ; Ppara protein, mouse ; Prescription Drugs ; oleuropein (2O4553545L) ; Cytochrome P-450 Enzyme System (9035-51-2)
    Language English
    Publishing date 2021-06-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.120.000302
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Oleuropein Promotes Neural Plasticity and Neuroprotection via PPARα-Dependent and Independent Pathways.

    Malliou, Foteini / Andriopoulou, Christina E / Kofinas, Aristeidis / Katsogridaki, Allena / Leondaritis, George / Gonzalez, Frank J / Michaelidis, Theologos M / Darsinou, Marousa / Skaltsounis, Leandros A / Konstandi, Maria

    Biomedicines

    2023  Volume 11, Issue 8

    Abstract: Oleuropein (OLE), a main constituent of olives, displays a pleiotropic beneficial dynamic in health and disease; the effects are based mainly on its antioxidant and hypolipidemic properties, and its capacity to protect the myocardium during ischemia. ... ...

    Abstract Oleuropein (OLE), a main constituent of olives, displays a pleiotropic beneficial dynamic in health and disease; the effects are based mainly on its antioxidant and hypolipidemic properties, and its capacity to protect the myocardium during ischemia. Furthermore, OLE activates the peroxisome proliferator-activated receptor (PPARα) in neurons and astrocytes, providing neuroprotection against noxious biological reactions that are induced following cerebral ischemia. The current study investigated the effect of OLE in the regulation of various neural plasticity indices, emphasizing the role of PPARα. For this purpose, 129/Sv wild-type (WT) and
    Language English
    Publishing date 2023-08-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11082250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Adrenoceptor-related decrease in serum triglycerides is independent of PPARα activation.

    Konstandi, Maria / Kypreos, Kyriakos E / Matsubara, Tsutomu / Xepapadaki, Eva / Shah, Yatrik M / Krausz, Kristopher / Andriopoulou, Christina E / Kofinas, Aristeidis / Gonzalez, Frank J

    The FEBS journal

    2019  Volume 286, Issue 21, Page(s) 4328–4341

    Abstract: Adrenoceptor (AR)-linked pathways belong to the major components of the stress response system and are associated with the pathophysiology of diseases within the spectrum of metabolic syndrome. In this study, the role of adrenoceptor stimulation in serum ...

    Abstract Adrenoceptor (AR)-linked pathways belong to the major components of the stress response system and are associated with the pathophysiology of diseases within the spectrum of metabolic syndrome. In this study, the role of adrenoceptor stimulation in serum triglyceride (TG) regulation in mice was investigated. For this purpose, α
    MeSH term(s) Adipose Tissue, White/drug effects ; Adipose Tissue, White/metabolism ; Adrenergic alpha-1 Receptor Agonists/pharmacology ; Animals ; Carrier Proteins/genetics ; Diacylglycerol O-Acyltransferase/genetics ; Forkhead Box Protein O1/genetics ; Gene Expression Regulation/drug effects ; Insulin/genetics ; Isoproterenol/pharmacology ; Liver/metabolism ; Mice ; Nuclear Receptor Subfamily 4, Group A, Member 1/genetics ; PPAR alpha/genetics ; Phenylephrine/pharmacology ; Phosphatidylinositol 3-Kinases/genetics ; Proto-Oncogene Proteins c-akt/genetics ; Receptors, Adrenergic, alpha-1/genetics ; Receptors, Adrenergic, beta-1/genetics ; Receptors, Adrenergic, beta-2/genetics ; Signal Transduction/drug effects ; Sterol Esterase/genetics ; Triglycerides/blood ; Triglycerides/metabolism
    Chemical Substances Adrenergic alpha-1 Receptor Agonists ; Carrier Proteins ; Forkhead Box Protein O1 ; Foxo1 protein, mouse ; Insulin ; Nr4a1 protein, mouse ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; PPAR alpha ; Receptors, Adrenergic, alpha-1 ; Receptors, Adrenergic, beta-1 ; Receptors, Adrenergic, beta-2 ; Triglycerides ; microsomal triglyceride transfer protein ; Phenylephrine (1WS297W6MV) ; Dgat1 protein, mouse (EC 2.3.1.20) ; Diacylglycerol O-Acyltransferase (EC 2.3.1.20) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Sterol Esterase (EC 3.1.1.13) ; Isoproterenol (L628TT009W)
    Language English
    Publishing date 2019-06-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.14966
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis.

    Konstandi, Maria / Sotiropoulos, Ioannis / Matsubara, Tsutomu / Malliou, Foteini / Katsogridaki, Alexandra / Andriopoulou, Christina E / Gonzalez, Frank J

    Psychopharmacology

    2019  Volume 236, Issue 6, Page(s) 1687–1699

    Abstract: Rationale: Stressful life events are suggested to contribute to the development of various pathologies, such as cardiovascular disorders, whose etiopathogenesis is highly associated with elevated levels of serum amyloid A (SAA) proteins. SAA synthesis ... ...

    Abstract Rationale: Stressful life events are suggested to contribute to the development of various pathologies, such as cardiovascular disorders, whose etiopathogenesis is highly associated with elevated levels of serum amyloid A (SAA) proteins. SAA synthesis in the liver is regulated by a complex network of cytokines acting independently or in concert with various hormones/stimulants including the stress-activated sympathetic nervous system.
    Objective: This study aims to investigate the underlying mechanisms that regulate the stress-induced hepatic synthesis of SAA, with particular focus on adrenoceptors (AR), major components of the sympathoadrenal response to stress.
    Methods and results: We demonstrated that repeated stress elevates IL-1β, IL-6, and TNFα serum levels in mice, accompanied by increased synthesis and secretion of hepatic SAA1/2 and SAA3, an effect that was blocked by AR antagonists. Moreover, stimulation of α
    Conclusion: Taken together, these findings strongly support a critical role of the AR-stimulated inflammatory response in the hepatic SAA production under stressful conditions, highlighting distinct AR type-specific mechanisms that regulate the hepatic synthesis of SAA1/2 and SAA3.
    MeSH term(s) Adrenergic Agonists/pharmacology ; Animals ; Cytokines/blood ; Inflammation Mediators/blood ; Interleukin-1beta/blood ; Liver/drug effects ; Liver/metabolism ; Male ; Mice ; Mice, 129 Strain ; Receptors, Adrenergic/metabolism ; Serum Amyloid A Protein/biosynthesis ; Stress, Psychological/blood ; Stress, Psychological/etiology ; Stress, Psychological/psychology ; Tumor Necrosis Factor-alpha/blood
    Chemical Substances Adrenergic Agonists ; Cytokines ; Inflammation Mediators ; Interleukin-1beta ; Receptors, Adrenergic ; Serum Amyloid A Protein ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2019-01-06
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 130601-7
    ISSN 1432-2072 ; 0033-3158
    ISSN (online) 1432-2072
    ISSN 0033-3158
    DOI 10.1007/s00213-018-5149-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Adrenoceptor‐related decrease in serum triglycerides is independent of PPARα activation

    Konstandi, Maria / Kypreos, Kyriakos E / Matsubara, Tsutomu / Xepapadaki, Eva / Shah, Yatrik M / Krausz, Kristopher / Andriopoulou, Christina E / Kofinas, Aristeidis / Gonzalez, Frank J

    FEBS journal. 2019 Nov., v. 286, no. 21

    2019  

    Abstract: Adrenoceptor (AR)‐linked pathways belong to the major components of the stress response system and are associated with the pathophysiology of diseases within the spectrum of metabolic syndrome. In this study, the role of adrenoceptor stimulation in serum ...

    Abstract Adrenoceptor (AR)‐linked pathways belong to the major components of the stress response system and are associated with the pathophysiology of diseases within the spectrum of metabolic syndrome. In this study, the role of adrenoceptor stimulation in serum triglyceride (TG) regulation in mice was investigated. For this purpose, α1‐ARs were activated with phenylephrine (PH) and β1/2‐ARs with isoprenaline (ISOP). Both AR agonists markedly reduced serum TG levels independently of PPARα activation. These drugs also significantly activated the hormone‐sensitive lipase in the white adipose tissue indicating increased mobilization of TGs in this tissue. In addition, PH and ISOP up‐regulated Lpl, Nr4A, Dgat1, Mttp, Aadac and Cd36 genes, critical in TG regulation, whereas the observed decrease in serum TG levels was independent of the hepatic very low‐density lipoprotein (VLDL)‐TG secretion. Interestingly, PH and ISOP also inactivated the hepatic insulin/PI3k/AKT/FoxO1 signaling pathway, holding a critical role in the regulation of genes involved in TG synthesis. Taken together, the findings of the present study indicate that stimulation of α1‐ and β1/2‐ARs markedly reduced serum TG steady‐state levels as a result of alterations in TG synthesis, uptake, transport, hydrolysis, metabolism and clearance, an effect induced by PPARα independent mechanisms.
    Keywords adrenergic receptors ; agonists ; blood serum ; carboxylic ester hydrolases ; gene expression regulation ; genes ; hydrolysis ; insulin ; isoprenaline ; metabolic syndrome ; metabolism ; mice ; pathophysiology ; peroxisome proliferator-activated receptor alpha ; phenylephrine ; phosphatidylinositol 3-kinase ; secretion ; signal transduction ; stress response ; triacylglycerols ; very low density lipoprotein ; white adipose tissue
    Language English
    Dates of publication 2019-11
    Size p. 4328-4341.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.14966
    Database NAL-Catalogue (AGRICOLA)

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