The Effect of Supervised Exercise Therapy on Mitochondrial Functionality and Thrombogenesis of Platelets in Patients with Peripheral Arterial Disease

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis that causes chronic narrowing of arteries and reduces capacity of blood flow to the legs of patients, which can precipitate acute thrombotic events. PAD leads to exercise intolerance that can progress in severity to greatly limit mobility. Advanced PAD may develop critical limb ischemia (CLI) and subsequently increase cardiovascular mortality. Supervised exercise training is a recommended first-line therapy for patients with PAD, which improves pain-free walking distance, functional status and quality of life, as well as, reduces cardiovascular risk factors and mortality. However, there is still controversy regarding the most effective exercise strategy for alleviating the disease progression in the PAD population. Platelets play a pivotal part in the progression of PAD and the genesis of complications. Platelets contain functional mitochondria, which are directly involved in the cell activation and apoptosis. An appreciation of how mitochondria contribute to platelet function obligates an understanding of the organelle function, fusion, and synthesis (biogenesis), as well as, fission and degradation (mitophagy). Assessment of platelet mitochondrial function has been utilized as a valuable tool to understand the basis of several human diseases. According to our previous studies, acute strenuous exercise increased platelet adhesion and aggregation whereas acute moderate exercise desensitized the platelet reactivity in healthy individuals and patients with cardiovascular disorder. In inflammatory thrombosis, exercise training effectively ameliorates platelet/neutrophil-promoted thrombin generation (TG) by down-regulating expression of procoagulant factors under hypoxic stress. However, what kind of exercise regimen optimally improves mitochondrial functionality of platelets and subsequently modulates platelet-mediated thrombogenesis in patients with PAD. Accordingly, we will conduct this three-year study that includes 1st year study: To establish the cell model of mitochondrial functionality (including oxidative phosphorylation, oxidative stress, fusion, fission, mitophagy and apoptosis) and thrombogenesis (TG) of platelets under atherosclerotic stimulation; 2nd year: The effects of PAD severity on mitochondrial functionality and thrombogenesis of platelets; and 3rd year study: The effect of supervised exercise therapy on mitochondrial functionality and thrombogenesis of platelets in patients with PAD. We expect that these results obtained from this study can aid in determining appropriate exercise intervention for simultaneously improving aerobic fitness and alleviating/retarding atherothrombotic progression in patients with PAD.

Project ID:PC10507-0256
External Project ID:MOST105-2314-B182-013-MY3