Silymarin own does not induce EC apoptosis and has been shown in several

reguation is a tered in the metabo ic syndrome, where CCG is impaired. MMPs are regu ated at the  eve  of both expression and activation. Severa  signa ing pathways have been shown to regu ate MMP expression and/or activation. Among these are the mitogen Silymarin activated protein kinases (MAPKs). MAPKs can be divided into the extraceuar signa -regu ated kinases (ERK1/2), p38 MAPK, and c-Jun N-termina  kinase (JNK) . The ERK1/2 pathway has been shown to regu ate expression and activation of many MMPs inc uding MMP 9 . p38 MAPK, when activated during inf ammation or the innate immune response,  ead to the activation of MMP 9 , and a sing e study imp icates p38 MAPK in the regu ation of MMP 9 activation in cu tured airway smooth musc e ces. However, it is not known which signa ing pathways may regu ate MMP expression and/or activation in co  atera  growth.

We have previous y shown that transient p38 MAPK activation on day 3 of RI is required for CCG in the norma  hea thy rat mode  where inhibition of p38 MAPK resu ted in ~60% reduction in RI-induced CCG. In addition, we have shown that RI-induced CCG was Voriconazole severe y compromised in the metabo ic syndrome JCR rat mode , and that this corre ated with  ack of RI-induced p38 MAPK activation [24]. However, the functiona  consequence of p38 MAPK activation in co  atera  growth remained unknown. Therefore the goa s of this study were to determine: 1) whether RI-induced activation of p38 MAPK regu ated the deve opment of coronary co  atera s through the activation of MMP 2 and 9 and the degradation of their ECM substrates, 2)whetherMMP 2 and 9were required for this ECM degradation and CCG, and 3) whether MMP 2 and/or 9 expression and/or activity were a tered in the metabo ic syndrome.

Tumor necrosis factor-(TNF ), a proinf ammatory cytokine that mediates apoptosis in supplier Rhein endothe ia  ces, is imp icated in the pathogenesis of atherosc erosis.1 A though it has been we   estab ished that endothe ia  ce (EC) apoptosis is an important process under ying the pathogenesis of atherosc erotic p aque,2 the mo ecu ar mechanisms responsib e for apoptosis of ECs in the setting of TNF  exposure remains e usive, because TNF  simu taneous y stimu ates pathways for apoptotic response (eg, caspase activation) and pathways for surviva  (eg, activation of the transcription factor NFB).3,4 The u timate fate of the ce is determined by the ba ance between pro- and antiapoptotic stimu i and is a consequence of cross-ta k between the major TNF -induced signa ing pathways.5,6 A c ue to so ving the identity of protective factors that are activated with TNF  in ECs has come from the ce cu ture mode ; ECs in vitro wi   not undergo apoptosis in the presence of TNF  un ess they primary care physician are sensitized by exposure to an inhibitor of protein synthesis such as cyc oheximide (CHX),7 a we  -known ribotoxin.8 Surprising y, a though CHX sensitizes ECs to apoptosis with TNF  exposure.

CHX on its own does not induce EC apoptosis and has been shown in severa  in vivo studies to protect the endothe ium from the formation atherosc erosis.9–11 This is supplier Taurine therefore an interesting paradox: a though TNF  on its own does not cause apoptosis of ECs and CHX a one has beneficia  effects on atherosc erosis, a combination of the 2  eads to EC apoptosis.

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