sRAGE attenuates angiotensin II-induced cardiomyocyte hypertrophy by inhibiting RAGE-NFκB-NLRP3 activation.

OBJECTIVE AND DESIGN:The receptor for advanced glycation endproducts is an innate immunity receptor that has been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, the possibility that signaling is involved in angiotensin II (Ang II)-induced cardiac left ventricular hypertrophy has yet to be investigated. We therefore determined whether has a role in regulating pathological cardiac hypertrophy. MATERIALS AND SUBJECTS:Protein abundance was estimated using Western blotting and intracellular level and phospho-p65 were detected using fluorescence microscopy. Enzyme-linked immunosorbent assay was used to detect HMGB1 and IL-1β. All in vitro experiments were performed using H9C2 cells. TREATMENTS:To induce cardiomyocyte hypertrophy, 300 nM Ang II was treated for 48 h and 2 µg/ml was treated 1 h prior to addition of Ang attenuated Ang II-induced cardiomyocyte hypertrophy by downregulating duanyu1648 and angiotensin II type 1 receptor expression. Secretion levels of high motility group box 1 and interleukin-1β, estimated from a cell culture medium, were significantly reduced by Activated and ERK1/2, important signals in left ventricular hypertrophy (LVH) development, were downregulated by sduanyu1648 treatment. Furthermore, we found that nuclear factor-κB and NOD-like receptor protein 3 (NLRP3) were associated with duanyu1648-mediated cardiomyocyte hypertrophy. CONCLUSIONS:In the context of these results, we conclude that duanyu1648 induces cardiac hypertrophy through the activation of the and NF-κB-NLRP3-IL1β signaling pathway, and suggest that may be an important mediator of Ang II-induced cardiomyocyte hypertrophy. In addition, we determined that inhibition of duanyu1648 activation with soluble duanyu1648 has a protective effect on Ang II-induced cardiomyocyte hypertrophy.

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