Role of 14-3-3 protein and oxidative stress in diabetic cardiomyopathy.
Cardiovascular disease is a leading cause of death worldwide. Diabetes mellitus is a well-known and important risk factor for cardiovascular diseases. The occurrence of diabetic cardiomyopathy is independent of hypertension, coronary artery disease, or any other known cardiac diseases. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Diabetic cardiomyopathy is characterized by morphologic and structural changes in the myocardium and coronary vasculature mediated by the activation of various signaling pathways. Myocardial apoptosis, hypertrophy and fibrosis are the most frequently proposed mechanisms to explain cardiac changes in diabetic cardiomyopathy. Mammalian 14-3-3 proteins are dimeric phosphoserine-binding proteins that participate in signal transduction and regulate several aspects of cellular biochemistry. 14-3-3 protein regulates diabetic cardiomyopathy via multiple signaling pathways. This review focuses on emerging evidence suggesting that 14-3-3 protein plays a key role in the pathogenesis of the cardiovascular complications of diabetes, which underlie the development and progression of diabetic cardiomyopathy.
Watanabe
Kenichi
K
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata City, Japan. watanabe@nupals.ac.jp
Thandavarayan
R A
RA
Gurusamy
N
N
Zhang
S
S
Muslin
A J
AJ
Suzuki
K
K
Tachikawa
H
H
Kodama
M
M
Aizawa
Y
Y
D048948:14-3-3 Proteins / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism* / Q000473:pathology; D048909:Diabetes Complications / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D015398:Signal Transduction
D048948:14-3-3 Proteins; D000804:Angiotensin II