Background:
Nucleoside diphosphate kinase B (NDPK-B) is an essential member of the NDPK family, which maintains nucleotide triphosphate homeostasis by catalyzing the transfer of a phosphate group between NTPs and NDPs. In addition, NDPK-B plays a distinct role in ion channel regulation and signal transduction. NDPK-B knockout (NDPK-B-KO) has been shown to result in vascular damage in the retina, leading to a diabetic retinopathy-like pathology. The present study aims to determine whether NDPK-B deficiency also induces cardiac damage resembling diabetic cardiomyopathy and the response of NDPK-B-deficient left ventricles (LVs) under hyperglycemia.
Materials and methods:
Male NDPK-B-KO and wild-type (WT) mice were used in this study. Type 1 diabetes mellitus was induced in the diabetic (DC) groups by intraperitoneal injection of 145 mg/kg body weight Streptozotocin. Three months after injection, blood glucose levels, HbA1c, and body weight were assessed. To evaluate cardiac function, echocardiography was performed. Accumulation of extracellular matrix was evaluated using Sirius Red staining in LVs on paraffin sections.
Results:
Diabetic NDPK-B-KO and WT mice displayed significantly reduced body weight and elevated blood glucose and HbA1c levels. Echocardiographic analysis demonstrated decreased mitral valve E’/A’ in both non-diabetic (NC) and DC NDPK-B-KO LVs compared with NC WT, similar to those observed in DC WT LVs, suggesting cardiac diastolic dysfunction in NDPK-B-KO mice. Furthermore, both DC WT and NC NDPK-B-KO LVs exhibited significantly enhanced collagen accumulation compared with NC WT LVs. Diabetes further aggravated this effect in DC NDPK-B-KO LVs.
Conclusion:
Our data demonstrate that NDPK-B deficiency impairs cardiac function and promotes extracellular matrix accumulation in the LVs. These findings indicate that NDPK-B plays a crucial role in maintaining proper cardiac function and the underlying mechanisms require further investigation.
