Objective To investigate the relationship between the box-2 of the high mobility group (HMGB2) and valve calcification in senile degenerative heart valve disease(SDHVD).METHODS:According to the echocardiographic results, patients with calcified heart valves were used as the experimental group and patients without calcified heart valves were used as the control group, and blood was drawn for testing, and serum levels of HMGB2 were measured by an ELISA assay. Human heart valve interstitial cells (hVIC) cultured in vitro were randomly divided into two groups. The calcification group was cultured with a medium containing calcificationinduction solution and cells were induced on days 1, 3, and 5, and the control group was cultured with a standard medium. Expression of bone morphogenetic protein 4 (BMP-4) and HMGB2 in both groups was detected by Western blot. RT-PCR was performed to detect the expression of the HMGB2 gene during calcification. The hVICs were cultured in vitro for 4 days with different concentrations of exogenous HMGB2 (0.01μg/ml,0.1μg/ml,1μg/ml,2μg/ml), while the control group was cultured with a standard medium and the expression of BMP-4 and NF- κBP65 was detected by Western blot. RESULTS: The serum level of HMGB2 was 7.90 (5.92,12.39) μg/L, higher than that of 7.06 (5.06,9.73) μg/L in the valve calcification group in elderly patients with degenerative valve disease (P = 0.005), the differences were statistically significant. In in vitro experiments, the cellular calcification protein BMP-4 and the HMGB2 protein were higher in the calcification group compared to the control group (P<0.05). Exogenous stimulation of hVICs with HMGB2 was able to up-regulate the expression of BMP-4 and NF-κBP65 (P<0.05). Conclusionss HMGB2 is correlated with valvular calcification in senile degenerative heart valve disease. The HMGB2 protein may promote the process of SDHVD valve calcification by activating the NF-κB pathway and upregulating the expression of BMP-4.