No abstract

These results demonstrate for the first time that preservation of GLP-1 using liraglutide or linagliptin is effective in inhibiting Ang II-induced cardiac fibrosis, suggesting that these drugs could be selected as an adjunctive therapy to improve clinical outcomes in the fibrosis-derived heart failure patients with or without diabetes.

Early growth response 1 (EGR-1) works as a master regulator that plays a key role in triggering inflammation-induced tissue injury after ischemia and reperfusion. This study tested the hypothesis that postconditioning (Postcon) or anti-inflammatory compound, curcumin, ameliorates inflammatory responses and further reduces infarct size by normalizing EGR-1 expression during reperfusion. In the control group, male Sprague-Dawley rats were subjected to 30-min ischemia and 180-min reperfusion. Postcon with four cycles of 10-s/10-s reperfusion/ischemia was applied at the onset of reperfusion. Curcumin (150 mg/kg per day) was fed 5 days before ischemia. Relative to the control, Postcon reduced expression of EGR-1 mRNA and protein, as further identified by less EGR-1 immunoreactivity in myocardial nuclei and microvessels during reperfusion. Along with EGR-1 downregulation, levels of plasma and myocardial tumor necrosis factor α and interleukin 6 (IL-6) were significantly decreased. Upregulated P-selectin and intercellular adhesion molecule 1 mRNA and protein as well as their immunoreactivity at area at risk myocardium were significantly attenuated. Neutrophil extravasation identified by myeloperoxidase immunohistochemical staining was inhibited. Infarct size, determined with triphenyltetrazolium chloride staining, was smaller in the Postcon group than that in the control. The protection achieved with pretreatment with curcumin was comparable to the benefits gained by Postcon in all end points measured. In H9C2 rat cardiomyoblast cell line, EGR-1 siRNA downregulated hydrogen peroxide-induced EGR-1 mRNA expression and subsequently reduced tumor necrosis factor α mRNA level. These results suggest that EGR-1 seems to play a critical role in myocardial reperfusion injury because downregulation of EGR-1 either by Postcon or the use of pharmacological intervention reduces infarct size, most likely through an inhibition of inflammation-mediated processes.

No abstract

Genistein plays an important role in the prevention of atherosclerosis. However, the underlying mechanisms have not been fully investigated. In this study, human umbilical vein endothelial cells (HUVECs) were pretreated with genistein (10, 100, and 1000 nM) for 6 h and then exposed to ox-LDL (50 mg/L) for another 24 h. Results showed that ox-LDL induced the expressions of E-selectin, P-selectin, monocyte chemotactic protein-1, interleukin-8, vascular adhesion molecule-1, and intercellular adhesion molecule-1, which were counteracted by genistein. The inhibitory effect was further enhanced with the augment of genistein (10, 100, and 1000 nM). Further analyses demonstrated the effect of genistein was associated with reducing miR-155 and elevating SOCS1, and miR-155 mimics or SOCS1 siRNA acted similarly in genistein ameliorating inflammation. Moreover, the effect of genistein was accompanied with the inhibition of the NF-ĸB signaling pathway. The present study indicates that genistein could reverse ox-LDL-induced inflammation through miR-155/SOCS1-mediated repression of the NF-ĸB signaling pathway in HUVECs.