The relationship between serum Wnt5a,MYL4,HDAC5 levels with cardiac function indicators,ventricular remodeling,and prognosis in patients with chronic heart failure

Liu Shikang

Li Juanli

Chen Tao

Wang Xin

She Jianqing

Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University

Abstract:Objective To discuss the relationship between serum wingless MMTV integration site family member5A(Wnt5a), cardiac myosin light chain 4(MYL4), histone deacetylase 5(HDAC5) levels and cardiac function indicators, ventricular remodeling, and prognosis in patients with chronic heart failure(CHF). Methods A total of 279 patients with CHF admitted to the Department of Cardiology, the First Affiliated Hospital of Xi'an Jiaotong University, from January 2023 to June 2024 were enrolled as the CHF group. All CHF patients were followed up for 1 year and then divided into a poor prognosis group(n = 86) and a good prognosis group(n = 193) according to their prognostic outcomes. During the same period, 168 healthy individuals who underwent physical examinations were selected as the control group. ELISA was used to measure serum Wnt5a, MYL4, and HDAC5 levels. Pearson correlation analysis was performed to evaluate the correlations between serum Wnt5a, MYL4, HDAC5 and cardiac function indicators and ventricular remodeling. Relative risk analysis was used to assess the impact of different serum Wnt5a, MYL4, and HDAC5 levels on prognosis. ROC curve analysis was used to evaluate the prognostic value of serum Wnt5a, MYL4, and HDAC5 levels. Additionally, DCA curve analysis was used to evaluate the clinical applicability of the predictive models. Results Serum Wnt5a and HDAC5 levels in the CHF group were significantly higher than those in the control group(t/P = 20.026/<0.001, 20.507/<0.001), while serum MYL4 level was significantly lower(t/P = 15.552/<0.001). Regarding prognostic stratification, the poor prognosis group had significantly higher levels of LVPWT,LVEDD, LAD, LVMI, serum Wnt5a, and HDAC5 compared to the good prognosis group(t/P = 9.603/<0.001, 12.742/<0.001,9.562/<0.001, 10.393/<0.001, 8.058/<0.001, 8.659/<0.001). In contrast, CO, LVEF, LVRI, and serum MYL4 levels were significantly lower in the poor prognosis group than in the good prognosis group(t/P = 11.741/<0.001, 10.261/<0.001, 6.857/<0.001, 7.388/<0.001). Correlation analysis showed that Wnt5a and HDAC5 were negatively correlated with CO, LVEF, and LVRI(r/P =-0.641/<0.001,-0.639/<0.001,-0.682/<0.001;-0.651/<0.001,-0.692/<0.001,-0.645/<0.001), and positively correlated with LVPWT, LVEDD, LAD, and LVMI(r/P = 0.603/<0.001, 0.597/<0.001, 0.587/<0.001, 0.582/<0.001; 0.561/<0.001, 0.534/<0.001, 0.539/<0.001, 0.506/<0.001). MYL4 was positively correlated with CO, LVEF, and LVRI(r/P = 0.652/<0.001, 0.671/<0.001, 0.674/<0.001), and negatively correlated with LVPWT, LVEDD, LAD, and LVMI(r/P =-0.584/<0.001,-0.596/<0.001,-0.553/<0.001,-0.517/<0.001). The risk of poor prognosis in patients with high levels of Wnt5a and HDAC5 was 1.623 times and 1.655 times higher than that in the low-level groups, respectively. The risk of poor prognosis in patients with low MYL4 level was 1.597 times higher than that in the high-level group. The AUC of the combination of serum Wnt5a,MYL4, and HDAC5 in predicting the prognosis of CHF patients was 0.937, and the combined prediction was superior to individual predictions(Z joint-Wnt5a = 4.690,Z joint-MYL4 = 4.008,Z joint-HDAC5 = 3.886, all P<0.001). The risk threshold probability ranged from 0.01 to 0.95, and the net benefit of the combined model in predicting the prognosis of CHF patients was higher than that of individual serum Wnt5a, MYL4, and HDAC5 levels. Conclusion Serum Wnt5a and HDAC5 levels are elevated, while MYL4 level is decreased in CHF patients. Combined detection of these three biomarkers can improve the predictive value for the prognosis of CHF patients.

Keyword:Chronic heart failureWingless MMTV integration site family member 5ACardiac myosin light chain 4Histone deacetylase 5Cardiac functionVentricular remodelingPrognosisCorrelation

Fund:Natural Science Foundation Research Program Project of Shaanxi Province (2025JC-JCQN-095)

Authors:*折剑青，E-mail:jianqingshe@xjtu.edu.cn;