New sniper assignment for a celebrity—role of endothelin-1 in diabetic cardiomyopathy

Abstract

Diabetic cardiomyopathy is a major threat to increased morbidity and mortality in population with diabetes. A number of hypotheses have been postulated for the pathogenesis of diabetic cardiomyopathy including defective polyol pathway, reduced energy production due to decrease in mitochondrial respiration and pyruvate dehydrogenase activity, accumulation of advanced glycation end-product (AGE) and free radical species, activation of protein kinase C (PKC) as well as enhanced hexosamine flux. These culprit machineries may result in impaired intracellular Ca²⁺ handling in cardiomyocytes due to compromised contractile and intracellular Ca²⁺ regulatory proteins such as myosin, titin, sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA), phospholamban and Na⁺–Ca²⁺ exchanger. Nevertheless, neither precise pathogenesis of the disease nor effective therapeutic remedy is available for diabetic cardiomyopathy. In this issue of JCRR, Ding et al. demonstrated an established role of endothelin-1 (ET-1) in diabetes-induced cardiomyocyte dysfunction using treatment of dual ET_A/ET_B receptor antagonist bosentan. Their results have conclusively consolidated the logic of ET-1 and its membrane receptors as a novel pathophysiological cue for the development of diabetic cardiomyopathy.