Involvement of Heparanase in Endothelial Cell-Cardiomyocyte Crosstalk.

ABSTRACT

Traditionally, the management of diabetes has focused mainly on controlling high blood glucose levels. Unfortunately, despite valiant efforts to normalize this blood glucose, poor medication management predisposes these patients to heart failure. Following diabetes, how the heart utilizes different sources of fuel for energy is key to the development of heart failure. The diabetic heart switches from using both glucose and fats, to predominately using fats as an energy resource for maintaining its activities. This transformation to using fats as an exclusive source of energy is helpful in the initial stages of the disease and is tightly controlled. However, over the progression of diabetes, there is a loss of this controlled supply and use of fats, which ultimately has terrible consequences since the uncontrolled use of fats produces toxic by-products which weaken heart function and cause heart disease. Heparanase is a key player that directs how much fats are provided to the heart and does so in association with several partners like LPL and VEGFs. Together, they regulate the amount of fats supplied, and their subsequent breakdown to provide energy. Following diabetes, there is a disruption in this network resulting in fat oversupply and cell death. Understanding how the heparanase-LPL-VEGFs "ensemble" cooperates, and its dysfunction in the diabetic heart would be useful in restoring metabolic equilibrium and limiting diabetes-related cardiac damage.