Treadmill exercise inhibited WNK2 to improve cardiac remodeling in diabetic cardiomyopathy
WANG Ting1, CAI Xueli1, LI Haiyan2, HUANG Zhouqing1, WANG Yonghua3
1.Department of Cardiology,the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; 2.Department of Rehabilitation, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China;3.Department of Physical Education, Wenzhou Medical University, Wenzhou 325035, China
WANG Ting,CAI Xueli,LI Haiyan, et al. Treadmill exercise inhibited WNK2 to improve cardiac remodeling in diabetic cardiomyopathy[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(6): 431-439,445.
Abstract：Objective: To investigate the effect of exercise training on preventing diabetic cardiomyopathy and to determine the role of WNK2 in high-glucose induced cardiomyocytes. Methods: Male db/db mice and C57BL/6 mice (as control) were fed a regular diet for 10 weeks, then began running exercise or remained sedentary
for 10 weeks. After that, cardiac function was assessed by echocardiography, and heart tissues were collected for further measurements including Hematoxylin-Eosin(HE) staining, Masson’s staining, wheat germ agglutinin (WGA) staining, real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In addition, after
pretreatment with WNK463 (a WNK2 inhibitor) in high glucose-induced H9C2 cardiomyocytes, the indicators of hypertrophy, fibrosis of cells, collagen type I (COL-I) and transforming growth factor β (TGF-β) were tested.Results: Compared with the control, the heart of db/db mice showed cardiac hypertrophy and fibrosis, reduced
cardiac function and increased WNK2 levels, with statistical difference (P<0.05). After 10 weeks of treadmill exercise, cardiac hypertrophy and collagen deposition were reversed, cardiac systolic function was improved, and WNK2 expression was decreased, showing significant difference (P<0.05). Mechanistically, WNK2 inhibition
prevented the expression of myosin heavy chain (MyHC) and atrial natriuretic peptide(ANP), as well as fibrosis reflected by matrix metalloprotein-9 (MMP9), collagen-I (COL-I) and transforming growth factor-β (TGF-β) in high glucose-stimulated cardiomyocytes, indicating that the suppression of WNK2 could reduce hypertrophy and fibrosis of cells. Conclusion: Running exercise limits cardiac hypertrophy, fibrosis and reverses cardiac dysfunction in diabetic cardiomyopathy by inhibiting WNK2 upregulation.
