Effects of Exercise Training on Platelet/Monocyte-Mediated Proliferation, Differentiation and Migration of Coronary Artery Smooth Muscle Cells in Patients with Heart Failure

Reduced exercise capacity negatively affects the ability of patients with heart failure (HF) to perform the activities required for daily life, further decreasing their independence and quality of life (QoL). Cardiac rehabilitation (CR) can effectively improve aerobic fitness and overall health status in patients with HF. However, there is still controversy regarding the most effective exercise strategy for alleviating the disease progression in the HF population. Coronary atherosclerosis, a chronic inflammatory process of lipid-rich lesion growth in the coronary artery, causes myocardial ischemia/infarction and consequently develops congestive HF. Vascular smooth muscle cell (VSMC) phenotypic modulation plays a key role in atherosclerosis and is classically defined as a switch from a 'contractile' phenotype to a 'synthetic' phenotype, whereby genes that define the contractile VSMC phenotype are suppressed and inflammation, proliferation and migratory mechanisms are induced. Monocyte and platelets are important participants at the various stages of atherosclerotic disease progression that include switching of VSMC phenotype and characteristics. Our previous investigations using sedentary males have demonstrated that exercise training reduced ox-LDL-induced production of reactive oxygen species and expression of adhesion molecules in monocyte, as well as, diminished the release and coagulation activity of platelet-derived microparticles. Recently, our clinical investigation in the HF population further revealed that aerobic interval training (AIT), rather than moderate continuous training (MCT), enhances ventilatory/hemodynamic efficiency and suppresses oxidative stress/inflammation associated with cardiac dysfunction. However, what kind of exercise regimen optimally alleviates atherosclerotic progression by influencing platelet/monocyte-mediated proliferation, differentiation and migration of coronary VSMC in the HF patients has not yet been established. Accordingly, we will conduct this three-year study that includes 1 st year study: To establish the cell model of platelet/monocyte-mediated proliferation, differentiation and migration of coronary VSMC; 2 nd year: The effects of AIT and MCT on platelet/monocyte-mediated proliferation, differentiation and migration of coronary VSMC in healthy sedentary individuals; and 3 rd year study: The effects of AIT and MCT on platelet/monocyte-mediated proliferation, differentiation and migration of coronary VSMC in patients with HF. We expect that these results obtained from this study can aid in determining appropriate exercise intervention for simultaneously improving aerobic fitness and alleviating/retarding atherosclerotic progression in patients with HF.

Project ID:PC10401-1126
External Project ID:MOST103-2314-B182-005-MY3