Role Of Toll-Like Receptor 4/NF-κB Signal In The Left Ventricle Remodeling Of Hypertension

Object: Left ventricular hypertrophy(LVH) is one of the most common target organ damages of hypertension. It has been considered as an independent risk factor for sudden cardiac death and ischemic heart disease and also as a basic mechanism of heart failure. To find an effective way to protect the target organ from injury in hypertension is an important strategy. Recently, inflammation has been demonstrated to play an important role in cardiac remodeling of hypertension, while it still needs more evidences and further study. NF-κB, as a nuclear transcription regulator, is well-known for its participating in inflammation, immunity, apoptosis and other biological process. Studies in vivo and in vitro have shown that NF-κB is necessary for cardiac hypertrophy induced by various hypertrophic stimuli. It has been noted that expression of a human homologue of Drosophila Toll, a transmembrane signaling protein linking innate immunity and adaptive immunity, now termed human Toll-like receptor 4 (TLR4), first identified as the receptor of lipopolysaccharide(LPS), appeared to be relatively high in the heart. Once activated by ligand, TLR4, the membrane receptor, initiates an intracellular kinase cascade that ultimately produces a translocation of NF-κB, a transcription factor known to activate a variety of inflammatory mediators and cytokines, from cytoplasm to nucleus. Most researches demonstrated that TLR4 played a critical role in the pathogenesis of viral myocarditis, septicemia, septic shock, atherosclerosis and other cardiovascular disease. While, whether TLR4 participated in the development of left ventricular remodeling of hypertension should be further investigated. Angiotensin II(Ang II), the effector peptide of the RAS (renin angiotensin system, RAS), is a pro-inflammation medium. The critical actions of Ang II are mediated primarily through the Ang II receptor subtype 1 (AT₁ receptor). Cardic local RAS contributed to the development of left ventricular remodeling of hypertension. Due...