Abstract：
:Macrovascular complications of diabetes, including diabetic cardiovascular disease (CVD), occur through a number of hyperglycaemia-induced mechanisms that include generation of oxidative stress, accumulation of advanced glycation end-products (AGE) and activation of protein kinase C (PKC). Cardiac oxidative stress is associated with increased cardiac fibrosis and hypertrophy, and reduced cardiac performance and contractility, leading to severe cardiac dysfunction and potentially fatal cardiac events. It occurs under conditions of excessive synthesis of reactive oxygen species (ROS). The ensuing activation of transcription factors such as nuclear factor-κB produces inflammation, fibrosis, hypertrophy and further oxidative stress, which itself causes DNA and membrane damage. This review summarises the mechanisms that generate ROS in the diabetic heart: mitochondrial electron leakage, activity of ROS-generating enzymes such as NADPH oxidase, xanthine oxidase and 12/15 lipoxygenase, uncoupling of nitric oxide synthase, accumulation of AGEs and activation of PKC. There is interaction between many of these ROS-generating pathways, with data from a range of published studies indicating that a common upstream pathway is the interaction of AGEs with their receptor (RAGE), which further promotes ROS synthesis. Therefore, agents targeted at decreasing ROS production have been investigated for prevention or treatment of diabetic CVD through reducing oxidative stress, and this review considers some of the studies carried out with anti-oxidant therapies and the feasibility of this approach for protecting against diabetic cardiomyopathy.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Faria A,Persaud SJdoi
10.1016/j.pharmthera.2016.11.013subject
Has Abstractpub_date
2017-04-01 00:00:00pages
50-62eissn
0163-7258issn
1879-016Xpii
S0163-7258(16)30239-Xjournal_volume
172pub_type
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