The aim of the study was to investigate the role of osteoprotegerin (OPG) in left ventricular hypertrophy (LVH) development in patients with essential hypertension (EH).A total of 1092 patients diagnosed with EH were recruited. The LVHs were determined and OPG gene polymorphisms were genotyped.Patients with LVH had a significantly higher mean serum OPG level than those without LVH. The 1181CC genotype carriers had significantly lower risk for LVH compared with GC and GG genotype carriers. The serum OPG level and OPG 1181 G>C polymorphism were found to be independent risk factors for the occurrence of LVH in hypertensive patients. In vitro study shows that OPG overexpression upregulates cell surface size, protein synthesis per cell, and hypertrophy- and fibrosis-related proteins in both cardiomyocytes and cardiac fibroblasts, whereas OPG inhibition can abolish the above-mentioned changes. Consistent with the in vitro data, our in vivo study revealed that the OPG administration induced the LVH in hypertensive rats.This study is the first to report the close association between OPG and LVH development in EH patients and the regulatory effect of OPG on cardiomyocytes and cardiac fibroblasts.

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Aim It has been reported that Osteoprotegerin (OPG) induces cardiomyocyte hypertrophy, but the mechanism remains unclear. This study was to investigate the role of Focal Adhesion Kinase (FAK) pathway in the OPG induced hypertrophy in cultured cardiomyocytes.Methods The H9C2 line of rat cardiomyocytes were treated with OPG at different concentrations and the cellular hypertrophy was evaluated. Meanwhile, the activity of FAK and other the phosphorylation kinases were detected. Autophagy flux assay was performed in absence and presence OPG. The interaction between proteins was analyses using Co-Immunoprecipitation assay.Results We found that OPG induced cardiomyocyte hypertrophic response, accompanied by dramatic increases a series of inflammatory factors and cytokines, as well as collagen synthesis. Also OPG inhibits autophagy and induces FAK phosphorylation. FAK silencing using si-RNA abrogates the effect of OPG on autophagy and cellular hypertrophy. Furthermore, Co-Immunoprecipitation assay reveals that OPG inhibits autophagy through enhancing the binding of FAK and Beclin1 Tyr 233.Conclusion The FAK/Beclin1 signal pathway is essential for the OPG induced autophagy inhibition and hypertrophic response in cultured H9C2 cells.