Regulation of Mitophagy by Low-Intensity Pulsed Ultrasound Attenuates Endothelial Dysfunction

Background: Diabetic vascular complications are a major cause of poor prognosis in patients with diabetes mellitus (DM). Mitophagy activation is a potential therapeutic target for type 2 diabetes mellitus (T2DM), but the role of low-intensity pulsed ultrasound (LIPUS) in this context remains unclear. Methods: The biological effects of LIPUS on endothelial cells under high glucose conditions were systematically evaluated using high glucose-treated human umbilical vein endothelial cells (HUVECs) and aortic tissues from diabetic rats as models, in combination with bioinformatics analysis and standard molecular and cellular biology techniques. Histological staining was further used to assess the protective role of LIPUS in the aortas of diabetic rats. Results: Bioinformatics analysis predicted that high glucose induces mitochondrial dysfunction, suppresses autophagy in HUVECs, impairs endothelial cell function, and activates fibroblasts. In vitro results were in agreement with these predictions. LIPUS treatment significantly counteracted these effects, restoring migration (p < 0.001) and angiogenesis (p < 0.05), increasing proliferation (p < 0.001), and decreasing apoptosis (p < 0.05). Mechanistically, LIPUS enhanced mitophagy, and its therapeutic effects were markedly diminished upon addition of the autophagy inhibitor 3-Methyladenine (3-MA). In vivo, LIPUS attenuated aortic endothelial damage and reduced collagen deposition in diabetic rats (p < 0.01). Conclusions: LIPUS may ameliorate hyperglycemia-induced endothelial cell dysfunction by activating mitophagy, and it also attenuates pathological damage in the abdominal aorta of diabetic rats, thereby providing experimental evidence for its application in the treatment of diabetic macrovascular complications.