No abstract

Background/Aims: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, has been shown to prevent cardiovascular diseases. Previously, Matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1) and toll-like receptor 4 (TLR4) were confirmed to play an important role in atherosclerosis and plaque instability. Both TLR4 and its negative regulator, Toll-interacting protein (Tollip), could be mediated by EGCG. The present study aimed to examine the effect of physiological concentration of EGCG (1 µM) on the expression of MMP-9 and MCP-1 in lipopolysaccharide (LPS)-induced macrophages and the potential mechanisms underlying its actions. Methods: The RAW264.7 cell line was used. Western blot was used to determine MCP-1, TLR4, Tollip, Mitogen-activated protein kinase (MAPK) and Nuclear factor-κB (NF-κB) protein expression. MMP-9 activity was assayed by gelatine zymography. The mRNA expression of MMP-9 and MCP-1 was measured by realtime polymerase chain reaction (RT-PCR). Results: EGCG (1 µM) significantly suppressed the expression of MMP-9 and MCP-1 and inhibited MAPK and NF-κB in LPS-induced macrophages but was blocked by Tollip silencing. The expression of LPS-induced MMP-9 and MCP-1 and the phosphorylation of the ERK1/2, P38 and NF-κB pathway proteins decreased after TLR4 siRNA treatment. Furthermore, EGCG mediated TLR4 and Tollip expression through binding to 67-kDa laminin receptor (67LR). Conclusion: The results of our study suggested that EGCG (1 µM) suppresses the TLR4/MAPK/NF-κB signalling pathway, decreases the expression of the plaque instability-mediating cytokines MMP-9 and MCP-1, and might prove to be effective in stabilizing atherosclerotic plaque.

Several studies have focused on the deleterious consequences of Right Ventricular Apical (RVA) pacing on Left Ventricular (LV) function, mediated by pacing-induced ventricular dyssynchrony. Therapeutic strategies to reduce the detrimental consequences of RVA pacing have been proposed, that includes upgrading of RVA pacing to Cardiac Resynchronization Therapy (CRT), alternative Right Ventricular (RV) pacing sites, minimal ventricular pacing strategies, as well as atrial-based pacing. In developing countries, single chamber RV pacing still constitutes a majority of cases of permanent pacing, and assessment of the optimal RV pacing site is of paramount importance. In chronically-paced patients, it is crucial to maintain as close and normal LV physiological function as possible, by minimizing ventricular dyssynchrony, reducing the chances for heart failure and other complications to develop. This review provides an analysis of the deleterious immediate and long-term consequences of RVA pacing, and the most recent available evidence regarding improvements in pacing options and strategies to optimize LV diastolic and systolic function. Furthermore, the place of advanced echocardiography in the identification of patients with pacing-induced LV dysfunction, the potential role of a new predictor of LV dysfunction in RV-paced subjects, and the long- term outcomes of patients with RV septal pacing will be explored.