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NRF2 in Cardiovascular Diseases: a Ray of Hope!
Ruju Vashi1, Bhoomika M Patel2
1Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat, 382481, India.
Abstract:
Heart failure is a worldwide pandemic influencing 26 million individuals worldwide and is expanding. Imbalanced redox homeostasis in cardiac cells alters the structure and function of the cells, which leads to contractile dysfunction, myocardial hypertrophy, and fibrosis in chronic heart failure. Various targets and agents acting on these such as siRNA, miRNA, interleukin-1, opioids, vasodilators, and SGLT2 inhibitors are being evaluated for heart failure, and nuclear factor erythroid 2-related factor 2 (NRF2) is one of them. NRF2 is a master transcription factor which is expressed in most of the tissues and exhibits a major role in amplification of the antioxidant pathways associated with the enzymes present in myocardium. Increased ROS generation and PI3K-Akt signaling can activate the receptor NRF2. Various in vitro and in vivo and few clinical studies suggested NRF2 may possess a potential for targeting oxidative stress-induced cardiovascular diseases including heart failures. All these studies collectively propose that upregulation of NRF2 will attenuate the increase in hemodynamic stress and provide beneficial role in cardiovascular diseases. The current review shall familiarize readers about the regulations and functions of NRF2. We have also discussed the current evidences suggesting beneficial role of NRF2 activators in heart failure. Graphical abstract.
Insights
Nuclear factor erythroid 2-related factor 2 (NRF2) shows promise in treating heart failure by combating oxidative stress. Upregulating NRF2 may attenuate hemodynamic stress and benefit cardiovascular diseases.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Cellular Physiology
Background:
- Heart failure is a growing global pandemic affecting millions.
- Imbalanced redox homeostasis in cardiac cells contributes to heart failure pathology, including contractile dysfunction, hypertrophy, and fibrosis.
- Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of antioxidant pathways in the myocardium.
Purpose of the Study:
- To review the regulation and function of NRF2.
- To discuss the evidence supporting NRF2 activators in treating heart failure.
- To explore NRF2's potential in targeting oxidative stress-induced cardiovascular diseases.
Main Methods:
- Review of in vitro, in vivo, and clinical studies on NRF2 in heart failure.
- Analysis of NRF2's role in antioxidant pathways and its activation by ROS and PI3K-Akt signaling.
- Examination of therapeutic strategies targeting NRF2.
Main Results:
- NRF2 plays a crucial role in amplifying myocardial antioxidant defense mechanisms.
- Activation of NRF2 can be triggered by increased reactive oxygen species (ROS) and PI3K-Akt signaling.
- Evidence suggests NRF2 upregulation attenuates hemodynamic stress and offers benefits in cardiovascular diseases.
Conclusions:
- NRF2 is a promising therapeutic target for heart failure and other cardiovascular diseases.
- Upregulating NRF2 may counteract the detrimental effects of oxidative stress in the heart.
- Further research into NRF2 activators could lead to novel heart failure treatments.
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