Recent Study Highlights the Impact of ApoA-IV on Diabetic Foot

 A recently published article in Experimental Biology and Medicine (Volume 248, Issue 8, April 2023) addresses the possible mechanisms by which Apolipoprotein A-IV (ApoA-IV) glycosylation exacerbates peripheral arterial atherosclerosis in patients with type 2 diabetes. The study, led by Dr. Tao Wang, Department of Thoracic and Cardiovascular Surgery, University of Chinese Academy of Science Shenzhen Hospital, utilizes a microfluidic real arterial chip model, using human internal mammary arteries to study the role of ApoA-IV glycosylation in diabetic peripheral atherosclerosis that can lead to diabetic foot syndrome. 

Diabetic foot is a serious complication in Type 2 diabetes. At least 30~40% of patients with diabetic foot must undergo amputation because of poor lower extremity microcirculation and complete occlusion of lower limb small arteries. Apolipoprotein A-IV is a lipid-binding protein, and animal studies have shown that it has a role in anti-atherosclerosis, prevention of platelet aggregation and thrombosis. Poor glycemic control in patients with long-term diabetes leads to glycosylation of ApoA-IV, which stimulates the peripheral arterial inflammation, which leads to the arteriosclerotic and prethrombotic state. It is possible to prevent and delay the occurrence and development of diabetic foot by lowering blood glucose, recombinant Apo A-IV therapy and limiting the glycation of Apo A-IV

The study, led by Dr. Wang, constructed a microfluidic arterial chip model that can precisely simulate real hemodynamics. They found that the glycated Apo A-IV from diabetic foot patients could significantly increase the production of tumor necrosis factor alpha in chip arteries, making the blood vessels more susceptible to atherosclerosis and thrombosis, which in Type 2 diabetic patients may lead to the development of diabetic foot. This work provides an experimental basis to further understand the pathogenesis of diabetic foot peripheral vascular disease. 

Dr. Wang said, "Diabetes is a complex chronic metabolic disease that takes time for it to develop into diabetic foot complications. In addition to changing daily living and eating habits, the most important thing is to control blood sugar in the prevention of diabetic foot. Long-term hyperglycemia can lead to an increase in advanced glycation end products in tissue, which may cause glycosylation of a variety of proteins including Apo A-IV, which induces formation of peripheral arterial atherosclerosis and promotes the development of diabetic foot. The pathogenesis of diabetic foot is still not clear, but Apo A-IV-glycosylation-induced diabetic peripheral arterial disease may be one of the important mechanisms of diabetic foot."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said, "This elegant study by Dr. Wang and colleagues uses a real human vascular organ on a chip model to study the mechanisms leading to diabetic peripheral arterial atherosclerosis that may eventually lead to diabetic foot syndrome. I see this microfluidic technology as a valuable tool for future studies on the pathogenesis of various vascular diseases and curative therapeutic approaches."

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Source: Experimental Biology and Medicine