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A Microfluidic System for Modeling Endothelial Dysfunction under Combined Physiological Pulsatile Shear Stress and Oscillatory Hyperglycemia
Published on: May 12, 2026
Influences of increased oxidative stress on endothelial function, platelets function, and fibrinolysis in
Hirofumi Tomiyama1, Toshio Kushiro, Ryo Okazaki
1Second Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan. tomiyama@tokyo-med.ac.jp
Insights
Glucose intolerance worsens oxidative stress and endothelial dysfunction in hypertensive patients. Vitamin C improved endothelial function and fibrinolysis in these patients, highlighting a potential therapeutic avenue.
Area of Science:
- Cardiovascular Medicine
- Metabolic Disorders
- Oxidative Stress Research
Background:
- Endothelial, platelet, and fibrinolytic functions are crucial in atherosclerosis.
- Glucose intolerance is known to impair endothelial function in hypertension.
- The precise mechanisms linking glucose intolerance, oxidative stress, and endothelial dysfunction require clarification.
Purpose of the Study:
- To investigate the impact of oxidative stress on endothelial function, platelet function, and fibrinolysis in hypertensive individuals with and without glucose intolerance.
- To elucidate the role of glucose intolerance in exacerbating these physiological processes.
- To assess the potential therapeutic effect of Vitamin C on these functions.
Main Methods:
- Categorized hypertensive patients into normal glucose metabolism (n=65) and glucose intolerance (n=47) groups based on an oral glucose tolerance test.
- Measured plasma thiobarbituric acid-reactive substances (TBARS) as a marker of oxidative stress.
- Assessed endothelial function via flow-mediated dilatation (FMD), platelet function (EC50), and fibrinolytic parameters before and after Vitamin C administration.
Main Results:
- Patients with glucose intolerance exhibited reduced FMD and elevated TBARS and fibrinolytic parameters compared to those with normal glucose metabolism.
- Vitamin C significantly improved FMD and reduced fibrinolytic parameters in the glucose intolerance group, but not in the normal metabolism group.
- Platelet function (EC50) remained similar between the groups.
Conclusions:
- Glucose intolerance exacerbates oxidative stress, leading to impaired endothelial function in hypertensive patients.
- These oxidative stress-induced abnormalities primarily affect fibrinolysis, not platelet function.
- Vitamin C demonstrates a potential to ameliorate endothelial dysfunction and fibrinolytic abnormalities associated with glucose intolerance in hypertension.
Abstract:
The effect of oxidative stress on endothelial function, platelet function, and fibrinolysis in hypertension with or without glucose intolerance was examined. The endothelium, platelets and fibrinolysis play important roles in the progression of atherosclerosis and interact with each other. We have previously demonstrated that glucose intolerance impairs endothelial function in hypertension, but its precise mechanisms have not been clarified. Hypertensive patients were divided by the results of 75-g oral glucose tolerance test into a normal glucose metabolism group (n = 65) and a glucose intolerance group (n = 47). The plasma level of thiobarbituric acid-reactive substances (TBARS) was assessed as a marker of oxidative stress. Endothelial function was assessed by flow-mediated dilatation (FMD), platelet function by the concentration of ADP dose inducing half-maximal aggregation (EC50), and fibrinolytic parameters by radioimmunoassay. These functions were assessed before and after acute administration of vitamin C. FMD was reduced while TBARS and fibrinolytic parameters were higher in patients with glucose intolerance than in those with a normal glucose metabolism. Vitamin C increased FMD and reduced fibrinolytic parameters significantly in the glucose intolerance group, but not in the group with normal glucose metabolism. On the other hand, the EC50 was similar in both groups. In conclusion, glucose intolerance aggravates oxidative stress, thereby contributing to the impairment of endothelial function in patients with hypertension. These abnormalities affect fibrinolysis but not platelet function.
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