Application of a Novel Curcumin Analog in the Management of Diabetic Cardiomyopathy

摘要

Diabetes mellitus is becoming an epidemic health threat and represents one of the most prevalent chronic non-communicable disorders. Cardiovascular complications are considered the leading cause of death for diabetic patients. Diabetes leads to undesired changes in cardiac structure and function, a condition commonly known as diabetic cardiomyopathy, which occurs independent of macro- and microvascular comorbidities in diabetes . Both systolic and diastolic dysfunctions have been demonstrated in diabetic hearts including prolonged duration of contraction and relaxation, reduced velocity of contraction and relaxation, and depressed myocardial contractility (1,3). In particular, clinical evaluation using electrocardiogram and echocardiography has revealed substantial functional changes in diabetic hearts, including shorter left ventricular ejection time, prolonged pre-ejection duration, increased wall stiffness, decreased fractional shortening, decreased rate of left ventricular filling, and increased action potential duration . To date, a plethora of cellular and molecular mechanisms have been postulated for the onset and development of diabetic cardiomyopathy, including reduced energy production due to decreases in mitochondrial respiration and pyruvate dehydrogenase activity, accumulation of reactive oxygen species, oxidative stress, apoptosis, impaired autophagy, and malfunction of cardiac contractile and in-tracellular Ca~(2+) regulatory proteins such as myosin, sarco/ endoplasmic reticulum Ca~(2+)-ATPase (SERCA), and Na~+-Ca~(2+) exchanger . The high morbidity and mortality for diabetic cardiomyopathy warrant aggressive clinical management involving lifestyle modification, control of glucose and lipid abnormalities, and treatment of hypertension and coronary artery diseases, if present. The commonly used therapeutic regimes in diabetic patients with heart anomalies encompass ACE inhibitors, digoxin, diuretics, β-blockers, Ca~(2+) antagonists, and spironolactone. Nonetheless, the mortality rate for diabetic cardiomyopathy still remains high, warranting novel and effective therapeutic strategies.