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Defective Nrf2-dependent redox signalling contributes to microvascular dysfunction in type 2 diabetes.
Gopal V Velmurugan1, Nagalingam R Sundaresan, Mahesh P Gupta
1Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Cardiovascular Research
|May 30, 2013
Summary
Type 2 diabetes impairs microvasculature function by depleting antioxidant capacity, leading to increased oxidative stress. Targeting the transcription factor Nrf2 with sulforaphane restores normal function by boosting antioxidant defenses.
Area of Science:
- Vascular Biology
- Oxidative Stress Research
- Diabetes Complications
Background:
- Type 2 diabetes is associated with depleted antioxidant defenses, increasing oxidative stress in microvasculature.
- This oxidative stress contributes to microvascular dysfunction, impacting blood flow regulation.
Purpose of the Study:
- To investigate how oxidative stress affects microvascular function in type 2 diabetes.
- To determine the role of the transcription factor Nrf2 in this process.
- To evaluate the therapeutic potential of targeting Nrf2.
Main Methods:
- Utilized pressure myography to assess myogenic constriction in mesenteric arterioles of diabetic (db/db) and non-diabetic (db/m) mice.
- Measured reactive oxygen species (ROS) production and Nrf2 pathway gene expression.
- Assessed the effects of glutathione (GSH) and the Nrf2 activator sulforaphane.
Main Results:
- Diabetic db/db mice exhibited enhanced myogenic constriction, correlated with elevated ROS and depleted Nrf2.
- Expression of Nrf2-regulated genes, including those for glutathione synthesis (GCLC, GCLM), and total GSH were significantly reduced in db/db vessels.
- Incubation with GSH restored normal myogenic function in db/db arterioles, while sulforaphane treatment normalized myogenic tone and reduced ROS in db/db mice.
Conclusions:
- Nrf2 depletion in type 2 diabetes compromises antioxidant capacity, leading to microvascular myogenic dysfunction.
- Pharmacological activation of Nrf2 with sulforaphane effectively reverses these functional deficits and reduces oxidative stress.
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