Platelet mitochondria dysfunction in diabetes mellitus: mechanisms and therapeutic implications

Platelets play a pivotal role in hemostasis, thrombosis, and inflammation, and their dysfunction in diabetes significantly contributes to vascular complications such as ischemic stroke, myocardial infarction, and peripheral artery disease. This review explores the mechanisms underlying platelet hyperactivity in diabetes, emphasizing the critical involvement of platelet mitochondria. Hyperglycemia, insulin resistance, oxidative stress, advanced glycation end products, calcium dysregulation, and protein kinase C activation all converge to impair platelet mitochondrial function, leading to increased reactive oxygen species, altered bioenergetics, and defective mitophagy. These changes promote a pro-thrombotic and pro-inflammatory state, exacerbating vascular injury. Furthermore, the review highlights emerging therapeutic strategies targeting platelet mitochondria, including pharmacological agents, mitochondrial antioxidants, and even mitochondrial transplantation, to restore platelet function and mitigate vascular risks in diabetic patients. Understanding the intricate relationship between platelet mitochondria and diabetes opens new avenues for preventing and treating diabetic vascular complications.