Published online Jul 27, 2014. doi: 10.5411/wji.v4.i2.116
Revised: May 10, 2014
Accepted: June 27, 2014
Published online: July 27, 2014
Processing time: 121 Days and 17 Hours
Cardiovascular diseases, especially atherosclerosis, found to be the dreadful diseases worldwide. There are diverse pathways associated with the progression of atherosclerosis. One of the important signaling pathways to target atherosclerotic plaque rupture is toll-like receptor 4 (TLR4) Pathway. Several studies are available for illustrating the role of TLR4 in health and diseases. Different types of immune cell are activated in atherosclerosis but primary cells that are activated by the TLR4 signaling are macrophages and endothelial cells. Mechanisms by which macrophages uptake lipids are diverse and it is very important to target signaling pathway responsible for controlling foam cell formation. The process of macrophages transformed foam cell formation is the critical event in progression of atherosclerotic lesion and TLR4 found to have actively participate in the event through mitogen activated protein kinases (MAPKs) activation. The activation of MAPKs signaling pathway leads to the accumulation of cholesterol in the macrophages and also contribute to the dissociation of IκB and the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 subunit, thereby activating key inflammatory cascade activation by MAPKs/NF-κB signaling pathway to induce toxicity by activating different inflammatory parameters. Hence, the review focussed on exploring the role of TLR4/MAPKs signaling pathway for the therapeutic inhibition of atherosclerosis.
Core tip: The inhibition of atherosclerosis is one of primary target for the therapeutics of cardiovascular diseases, which is the eminent health problem worldwide. The important function of toll-like receptor 4 (TLR4) in the activation and progression of atherosclerosis is justified here. The TLR4 in turn activates the mitogen activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells which are responsible for most of the inflammatory events. Hence, therapeutic inhibition of TLR4/MAPKs signaling pathway is one of the best method of inhibiting atherosclerosis.