Browsing by Author "Krause, Bernardo"

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    Characterization of the active response of a guinea pig carotid artery
    (2022) Navarrete, Alvaro; Varela, Pablo; Lopez, Miguel; Garcia-Herrera, Claudio M.; Celentano, Diego J.; Krause, Bernardo
    This work presents a characterization of the active response of the carotid artery of guinea pig fetuses through a methodology that encompasses experiments, modeling and numerical simulation. To this end, the isometric contraction test is carried out in ring samples subjected to different levels of KCl concentrations and pre-stretching. Then, a coupled mechanochemical model, aimed at describing the smooth cell behavior and its influence on the passive and active mechanical response of the vascular tissue, is calibrated from the experimental measurements. Due to the complex stress and strain fields developed in the artery, a finite element numerical simulation of the test is performed to fit the model parameters, where those related to the phosphorylation and dephosphorylation activity along with the load-bearing capacity of the myosin cross-bridges are found to be the most predominant when sensitizing the active response. The main strengths of the model are associated with the prediction of the stationary state of the active mechanical response of the tissue through a realistic description of the mechanochemical process carried out at its cellular level.
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    Epigenetics: New Concepts of Old Phenomena in Vascular Physiology
    (BENTHAM SCIENCE PUBL LTD, 2009) Krause, Bernardo; Sobrevia, Luis; Casanello, Paola
    The hypothesis of 'Developmental Origins of Health and Disease' (DOHaD) relies on the presence of mechanisms sensing and signalling a diversity of stimuli during fetal development. The mechanisms that have been broadly suggested to be involved in these processes are the epigenetic modifications that could 'record' perinatal stimuli. Since the definition of epigenetic and the associated mechanisms are conflictive, in this review epigenetic was defined as 'chromosome-based mechanisms that can change the phenotypic plasticity in a cell or organism'. The most understood epigenetic mechanisms (i.e. DNA methylation, histone post-translational modifications (PTM), ATP-dependent chromatin modifications and non-coding RNAs) and reported evidence for their role in fetal programming were briefly reviewed.
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    FOETAL AND UMBILICAL VASCULAR REACTIVITY IN A MODEL OF IUGR THROUGH GRADUAL UTERINE ARTERY OCCLUSION IN GUINEA PIGS
    (W B SAUNDERS CO LTD, 2014) Scheneider, Daniela; Alegria, Rene; Herrera, Emilio; Farias, Marcelo; Casanello, Paola; Krause, Bernardo
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    High D-Glucose reduces SLC29A1 promoter activity and adenosine transport involving specific protein 1 in human umbilical vein endothelium
    (WILEY, 2008) Puebla, Carlos; Farias, Marcelo; Gonzalez, Marcelo; Vecchiola, Andrea; Aguayo, Claudio; Krause, Bernardo; Pastor Anglada, Marcal; Casanello, Paola; Sobrevia, Luis
    High D-glucose reduces human equilibrative nucleoside transporter 1 (hENT1)-mediated adenosine uptake involving endothelial nitric oxide synthase (eNOS), mitogen-activated protein (MAP) kinase kinases 1 and 2/MAP kinases p42/44 (MEK/ERKs), and protein kinase C (PKC) activation in human umbilical vein endothelium (HUVEC). Since NO represses SLC29A1 gene (hENT1) promoter activity we studied whether D-glucose-reduced hENT1-adenosine transport results from lower SLC29A1 expression in HUVEC primary cultures. HUVEC incubation (24 h) with high D-glucose (25 mM) reduced hENT1-adenosine transport and pGL3-hENT1(-1114) construct SLC29A1 reporter activity compared with normal D-glucose (5 mM). High D-glucose also reduced pGL3-hENT1(-1114) reporter activity compared with cells transfected with pGL3-hENT1(-795) Construct. N-G-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor), PD-98059 (MEK1/2 inhibitor), and/or calphostin C (PKC inhibitor) blocked D-glucose effects. Insulin(1 nM) and phorbol 12-myristate 13-acetate (PMA, 100 nM, PKC activator), but not 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD, 100 nM, PMA less active analogue) reduced hENT1-adenosine transport. L-NAME and PD-98059 blocked insulin effects. L-NAME, PD-98059, and calphostin C increased hENT1 expression without altering protein or mRNA stability. High D-glucose increased Sp1 transcription factor protein abundance and binding to SLC29A1 promoter, phenomena blocked by L-NAME, PD-98059, and calphostin C. Sp1 overexpression reduced SLC29A1 promoter activity in normal D-glucose, an effect reversed by L-NAME and further reduced by S-nitroso-N-acetyl-L,D-penicillamine (SNAP, NO donor) in high D-glucose. Thus, reduced hENT1 -mediated adenosine transport in high D-glucose may result from increased Sp1 binding to SLC29A1 promoter down-regulating hENT1 expression. This phenomenon depends on eNOS, MEK/ERKs, and PKC activity, suggesting potential roles for these molecules in hyperglycemia-associated endothelial dysfunction.