Rosiglitazone Restores Endothelial Dysfunction in a Rat Model of Metabolic Syndrome through PPARγ- and PPARδ-Dependent Phosphorylation of Akt and eNOS

Vascular endothelial dysfunction has been demonstrated in metabolic syndrome (MS). Chronic administration of rosiglitazone ameliorates endothelial dysfunction through PPARγ-mediated metabolic improvements. Recently, studies suggested that single dose of rosiglitazone also has direct vascular effects, but the mechanisms remain uncertain. Here we established a diet-induced rat model of MS. The impaired vasorelaxation in MS rats was improved by incubating arteries with rosiglitazone for one hour. Importantly, this effect was blocked by either inhibition of PPARγ or PPARδ. In cultured endothelial cells, acute treatment with rosiglitazone increased the phosphorylation of Akt and eNOS and the production of NO. These effects were also abolished by inhibition of PPARγ, PPARδ, or PI3K. In conclusion, rosiglitazone improved endothelial function through both PPARγ- and PPARδ-mediated phosphorylation of Akt and eNOS, which might help to reconsider the complex effects and clinical applications of rosiglitazone

TRPV1 Activation Attenuates High-Salt Diet-Induced Cardiac Hypertrophy and Fibrosis through PPAR- δ

High-salt diet-induced cardiac hypertrophy and fibrosis are associated with increased reactive oxygen species production. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, exerts a protective role in cardiac remodeling that resulted from myocardial infarction, and peroxisome proliferation-activated receptors δ (PPAR-δ) play an important role in metabolic myocardium remodeling. However, it remains unknown whether activation of TRPV1 could alleviate cardiac hypertrophy and fibrosis and the effect of cross-talk between TRPV1 and PPAR-δ on suppressing high-salt diet-generated oxidative stress. In this study, high-salt diet-induced cardiac hypertrophy and fibrosis are characterized by significant enhancement of HW/BW%, LVEDD, and LVESD, decreased FS and EF, and increased collagen deposition. These alterations were associated with downregulation of PPAR-δ, UCP2 expression, upregulation of iNOS production, and increased oxidative/nitrotyrosine stress. These adverse effects of long-term high-salt diet were attenuated by chronic treatment with capsaicin. However, this effect of capsaicin was absent in TRPV1−/− mice on a high-salt diet. Our finding suggests that chronic dietary capsaicin consumption attenuates long-term high-salt diet-induced cardiac hypertrophy and fibrosis. This benefit effect is likely to be caused by TRPV1 mediated upregulation of PPAR-δ expression

On c=1 matrix model and 2D gravity - with emphasis on chiral formalism

In this thesis, we study the relationship between the effective spacetime theory of Liouville string theory in two spacetime dimensions and the collective field of the c=1 matrix model by finding exact solutions on both sides. The correspondence between the matrix model and the effective spacetime theory turns out to be nonlinear in their fields. By comparing the exact solutions on both side, we show the nonlinearity begins to appear at the second order in terms of the incoming tachyon field. In particular, we employ the chiral formalism in the matrix model the formalism allowing to write down solutions to equations of motion explicitly — to find out exact solutions. We show the chiral formalism is much simpler than the more traditional classical field method. Also it is more powerful as it enables us to study the behavior around the singular point in the background of the matrix model.Science, Faculty ofPhysics and Astronomy, Department ofGraduat

Gravitational collapse and black hole formation in a braneworld

In this thesis we present the first numerical study of gravitational collapse in braneworld within the framework of the single brane model by Randall-Sundrum (RSII). We directly show that the evolutions of sufficiently strong initial data configurations result in black holes (BHs) with finite extension into the bulk. The extension changes from sphere to pancake (or cigar, as seen from a different perspective) as the size of BH increases. We find preliminary evidences that BHs of the same size generated from distinct initial data profiles are geometrically indistinguishable. As such, a no-hair theorem of BH (uniqueness of BH solution) is suggested to hold in the RSII spacetimes studied in this thesis—these spacetimes are axisymmetric without angular momentum and non-gravitational charges. In particular, the BHs we obtained as the results of the dynamical system, are consistent with the ones previously obtained from a static vacuum system by Figueras and Wiseman. We also obtained some results in closed form without numerical computation such as the equality of ADM mass of the brane with the total mass of the braneworld. The calculation within the braneworld requires advances in the formalism of numerical relativity (NR). The regularity problem in previous numerical calculations in axisymmetric (and spherically symmetric) spacetimes, is actually associated with neither coordinate systems nor the machine pre- cision. The numerical calculation is regular in any coordinates, provided the fundamental variables (used in numerical calculations) are regular, and their asymptotic behaviours at the vicinity of the axis (or origin) are compatible with the finite difference scheme. The generalized harmonic (GH) formalism and the BSSN formalism for general relativity are developed to make them suitable for calculations in non-Cartesian coordinates under non-flat background. A conformal function of the metric is included into the GH formalism to simulate the braneworld.Science, Faculty ofPhysics and Astronomy, Department ofGraduat