King's College London

Research portal

Cardiac oxidative stress in diabetes: Mechanisms and therapeutic potential

Research output: Contribution to journalArticlepeer-review

Alyssa Faria, Shanta J Persaud

Original languageEnglish
JournalPharmacology and Therapeutics
Early online date1 Dec 2016
DOIs
Accepted/In press8 Nov 2016
E-pub ahead of print1 Dec 2016

Documents

King's Authors

Abstract

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.

Download statistics

No data available

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454