Title : The protective role of Nicotinamide Adenine Dinucleotide in diabetic cardiomyopathy from db/db mice.
Abstract:
Diabetic cardiomyopathy (DCM) is one of the type 2 diabetes complications, usually accompanied by changes in myocardial structure and function. Nicotinamide adenine dinucleotide (NAD+), a critical coenzyme present in every living cell, is involved in a myriad of metabolic processes associated with cellular bioenergetics. NAD+ participates various processes that are dysregulated in cardiovascular diseases. Our study investigated the effect of NAD+ in DCM and underlying mechanism. Male C57BL/6 mice and db/db mice at 12 weeks of age were randomly divded into four groups (n = 8/group): C57BL/6J group; C57BL/6J + NAD+ group, db/db group and db/db + NAD+ group. NAD+ (2mg/kg/day) was administrated for treatment. Each group of mice was subjected to their respective treatment for 16 weeks. After 16 weeks, echocardiography, serum analysis, histological tests, and protein detection were performed. The metabolic characteristics of the mice showed that NAD+ significantly attenuated body weight and serum MDA, triglycerides (TG), total cholesterol (TC) levels. Echocardiography also confirmed that NAD+ supplementation ameliorates cardiac dysfunction by increased ejection fraction (EF) and fractional shortening (FS). In histologically, NAD+ reduced myocardial tissue damage (HE staining) and myocardial cell hypertrophy (WGA staining). NAD+ supplementation reduced oxidative stress (SIRT1, SIRT3, NRF2, SOD ), endothelial dysfunction(ICAM-1, eNOS, iNOS, ET), lipid deposition(CD36, CD68, LOX-1, PPAR-γ), apoptosis(BAX, BCL-XL, Caspase-1, Caspase-8) and fibrosis (collagen I, collagen III, Smad3, TGF-β) in Diabetes cardiomyopathy. These results strongly suggest that NAD+ played a role in diabetic cardiomyopathy treatment and provided a promising new therapeutic agent against diabetic cardiomyopathy.
Key words: Nicotinamide adenine dinucleotide; Diabetic cardiomyopathy; db/dbmice; oxidative stress
Audience Takeaway:
- Diabetes mellitus (DM) and diabetic complications has to be a major global public health problem, and affecting 415 million peoples grobally. Macrovasculature and microvascular injuries were considers as the major complications of DM. There were 65% of DM patients dying from CVD complications despite numerous advances in treatment. With more in-depth studies, many researches have been suggested that glucose is no longer the single factor contributing to diabetic complications. Rather, dyslipidemia, inflammation and obesity et al. have deeply affected the occurrence and development of diabetic complications. Our studies showed that the mechanism of macrovasculature and microvascular injuries of DM.
- Our results demonstrate that NAD+ played a role in diabetic cardiomyopathy treatment and provided a promising new therapeutic agent against diabetic cardiomyopathy. Other faculty could use to expand their research in the treatment of other cardiovascular diseases with NAD.
- It has a good safety, and its role in oxidative stress, endothelial dysfunction, and lipid deposition, which can useful the macrovascular and microvascular diseases caused by diabetes cardiomyopathy.
