Global knockout of Vegfb in rats with STZ-induced diabetes increased cardiac lipoprotein lipase activity, protected against dyslipidemia, and reduced cardiac cell death compared to wildtype diabetic rats.
Does global Vegfb knockout improve cardiac lipoprotein lipase activity and protect against diabetic cardiomyopathy in rats with STZ-induced diabetes?
Global knockout of VEGFB in a rat model of Type 1 diabetes improves cardiac LPL activity and lipid profiles, offering a potential mechanism-based therapeutic approach for diabetic cardiomyopathy.
Diabetes affects over half a billion people worldwide, with cardiovascular disease being its leading cause of death, either occurring secondary to atherosclerosis or due to an intrinsic defect in heart muscle (diabetic cardiomyopathy, DbCM). One instigator for DbCM is impaired cardiac metabolism characterized by excessive fatty acid (FA) delivery and utilization by the heart, causing oxidative stress and toxic lipid accumulation. Inhibition of vascular endothelial growth factor B (VEGFB) has been shown to counter these factors associated with abnormal cardiac metabolism by inducing metabolic flexibility and preventing cardiac lipid accumulation in Type 2 diabetes. However, its impact on lipoprotein lipase (LPL) and the sources of FA for cardiac use in Type 1 diabetes is unknown. Global Vegfb knockout (Vegfb KO ) in rats caused limited phenotype and cardiac transcriptome changes under normal conditions but notably reduced cardiac LPL activity, probably by impeding LPL translocation from cardiomyocyte to the coronary vasculature. Under streptozotocin (STZ)-induced diabetes, Vegfb KO rats exhibited increased cardiac LPL activity, protecting animals from dyslipidemia, decreased plasma saturated FA, and provided a safer cardiac FA source, LPL-derived FA. Knockout of Vegfb also protected animals from DbCM by inhibiting excess FA oxidation, preserving angiogenesis and alleviating cell death in the heart. Inhibiting VEGFB may offer a promising therapeutic approach to address the current lack of mechanism-based treatments for DbCM.
Wang et al. (Wed,) conducted a other in Type 1 Diabetes (STZ-induced). Global Vegfb knockout vs. Wildtype was evaluated on Cardiac lipoprotein lipase (LPL) activity and plasma lipid profile. Global knockout of Vegfb in rats with STZ-induced diabetes increased cardiac lipoprotein lipase activity, protected against dyslipidemia, and reduced cardiac cell death compared to wildtype diabetic rats.