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Clinical and Experimental Study of High Mobility Group Box-2 and Valvular Calcification in Elderly Patients with
Hongtao Huang1, Qingpiao Sun2, Yu Huang3
1Nantong University Medical School, Nantong, China, 2013320091@stmail.ntu.edu.cn.
Insights
High mobility group box-2 (HMGB2) is linked to valve calcification in senile degenerative heart valve disease. HMGB2 may promote calcification by activating the NF-κB pathway and increasing BMP-4 expression.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biochemistry
Background:
- Senile degenerative heart valve disease (SDHVD) is a growing clinical concern.
- Valve calcification is a key pathological feature of SDHVD, leading to significant morbidity.
- The molecular mechanisms underlying SDHVD valve calcification require further elucidation.
Purpose of the Study:
- To investigate the association between high mobility group box-2 (HMGB2) and valve calcification in SDHVD.
- To explore the potential role of HMGB2 in the pathogenesis of SDHVD valve calcification.
Main Methods:
- Serum HMGB2 levels were measured in patients with and without calcified heart valves using ELISA.
- Human heart valve interstitial cells (hVICs) were cultured in vitro and subjected to calcification induction.
- Protein and gene expression of HMGB2, BMP-4, and NF-κB P65 were analyzed using Western blot and RT-PCR.
Main Results:
- Serum HMGB2 levels were significantly higher in patients with calcified heart valves compared to controls.
- In vitro, HMGB2 protein and BMP-4 expression were elevated in the calcification group of hVICs.
- Exogenous HMGB2 administration upregulated BMP-4 and NF-κB P65 expression in hVICs.
Conclusions:
- HMGB2 is correlated with valvular calcification in SDHVD.
- HMGB2 may promote SDHVD valve calcification by activating the NF-κB pathway.
- HMGB2's upregulation of BMP-4 suggests a key role in the calcification process.
Introduction:
The aim of this study was to investigate the relationship between the high mobility group box-2 (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; blood was drawn for testing, and serum levels of HMGB2 were measured by an enzyme-linked immunosorbent assay. Human heart valve interstitial cells (hVICs) cultured in vitro were randomly divided into two groups. The calcification group was cultured with a medium containing calcification induction 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 (0.01 μg/mL, 0.1 μg/mL, 1 μg/mL, 2 μg/mL), while the control group was cultured with a standard medium and the expression of BMP-4 and NF-κB P65 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 upregulate the expression of BMP-4 and NF-κB P65 (p < 0.05).
Conclusions:
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.
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