Abstract
Diabetic cardiomyopathy is one of the main causes of heart failure and death in patients with diabetes mellitus. Reactive oxygen species produced excessively in diabetes mellitus cause necrosis, apoptosis, ferroptosis, inflammation, and fibrosis of the myocardium as well as impair the cardiac structure and function. It is increasingly clear that oxidative stress is a principal cause of diabetic cardiomyopathy. The transcription factor nuclear factor-erythroid 2 p45-related factor 2 (NRF2) activates the transcription of more than 200 genes in the human genome. Most of the proteins translated from these genes possess anti-oxidant, anti-inflammatory, anti-apoptotic, anti-ferroptotic, and anti-fibrotic actions. There is a growing body of evidence indicating that NRF2 and its target genes are crucial in preventing high glucose-induced oxidative damage in diabetic cardiomyopathy. Recently, many natural and synthetic activators of NRF2 are shown to possess promising therapeutic effects on diabetic cardiomyopathy in animal models of diabetic cardiomyopathy. Targeting NRF2 signaling by pharmacological entities is a potential approach to ameliorating diabetic cardiomyopathy. However, the persistent high expression of NRF2 in cancer tissues also protects the growth of cancer cells. This “dark side” of NRF2 increases the challenges of using NRF2 activators to treat diabetic cardiomyopathy. In addition, some NRF2 activators were found to have off-target effects. In this review, we summarize the current status and challenges of NRF2 as a potential therapeutic target for diabetic cardiomyopathy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 512-520 |
| Number of pages | 9 |
| Journal | International heart journal |
| Volume | 60 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2019 |
Funding
From the 1Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China, 2Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA and 3Department of Anesthesiology, The University of Hong Kong, Hong Kong, China. This work was supported, in part, by a research grant 81770831 (to Dr. Zhi-Dong Ge) from the National Science Foundation of China, Beijing, The People’s Republic of China. Address for correspondence: Zhi-Dong Ge, MD, Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. E-mail: [email protected] Received for publication August 7, 2018. Revised and accepted November 2, 2018. Released in advance online on J-STAGE April 10, 2019. doi: 10.1536/ihj.18-476 All rights reserved by the International Heart Journal Association.
Keywords
- Cancer
- Diabetes mellitus
- Reactive oxygen species
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
