Role of the cathepsin K/Calcineurin/Nuclear factor of activated T-cells axis in the pathogenesis and management of diabetic cardiomyopathy

Abstract

Diabetes mellitus has become a devastating global epidemic. Patients with diabetes suffer a high prevalence of diabetic cardiomyopathy (DCM). DCM is a type of cardiac problem independent of any preexisting macro- and micro-vascular diseases. The pathophysiological basis underlying diabetes-induced cardiac damage is rather complex and multifactorial. Although a number of risk factors including oxidative stress, apoptosis, and aberrant intracellular Ca2+ metabolism have been postulated to play a role in the onset and development of cardiac anomalies within diabetes, the precise mechanisms responsible for DCM remain elusive. This mini-review discusses the latest findings of mechanisms involved in the progression of cardiomyopathy in diabetes. We emphasize the role of the lysosomal cysteine protease, cathepsin K, and its downstream calcineurin/nuclear factor of activated T-cells signaling in the prevention and treatment of DCM.

Keywords

• Calcineurin
• cardiomyopathy
• cathepsin K
• diabetes
• heart failure
• nuclear factor of activated T-cells