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Effects of high-amount–high-intensity exercise on in vivo platelet activation: Modulation by lipid peroxidation and AGE/RAGE axis

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH13-04-0295
Issue: 2013: 110/6 (Dec) pp. 1087-1307
Pages: 1232-1240

Effects of high-amount–high-intensity exercise on in vivo platelet activation: Modulation by lipid peroxidation and AGE/RAGE axis

Online Supplementary Material

F. Santilli (1), N. Vazzana (1), P. Iodice (2), S. Lattanzio (1), R. Liani (1), R. G. Bellomo (3), G. Lessiani (1), F. Perego (4), R. Saggini (2), G. Davì (1)

(1) Internal Medicine and Center of Excellence on Aging, “G. d’Annunzio” University of Chieti, Chieti, Italy; (2) Department of Neuroscience and Imaging, “G. d’Annunzio” University of Chieti, Chieti, Italy; (3) Department of Human Movement, “G. d’Annunzio” University of Chieti; (4) Internal Medicine III, Luigi Sacco Hospital, University of Milan, Milan, Italy

Keywords

oxidative stress, platelet activation, esRAGE, Aerobic exercise

Summary

Physical activity is associated with cardiovascular risk reduction, but the effects of exercise on platelet activation remain controversial. We investigated the effects of regular high-amount, high intensity aerobic exercise on in vivo thromboxane (TX)-dependent platelet activation and plasma levels of platelet-derived proteins, CD40L and P-selectin, and whether platelet variables changes may be related to changes in high-density lipoprotein (HDL) and in the extent of oxidative stress and oxidative stress-related inflammation, as reflected by urinary isoprostane excretion and endogenous soluble receptor for advanced glycation end-products (esRAGE), respectively. Urinary excretion of 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F2α and plasma levels of P-selectin, CD40L and esRAGE were measured before and after a eight-week standardised aerobic high-amount–high-intensity training program in 22 sedentary subjects with low-to-intermediate risk. Exercise training had a clear beneficial effect on HDL cholesterol (+10%, p=0.027) and triglyceride (-27%, p=0.008) concentration. In addition, a significant (p<0.0001) decrease in urinary 11-dehydro-TXB2 (26%), 8-iso-PGF2α (21%), plasma P-selectin (27%), CD40L (35%) and a 61% increase in esRAGE were observed. Multiple regression analysis revealed that urinary 8-iso-PGF2α [beta=0.33, SEM=0.116, p=0.027] and esRAGE (beta=-0.30, SEM=31.3, p=0.046) were the only significant predictors of urinary 11-dehydro-TXB2 excretion rate over the training period. In conclusion, regular high-amount–high-intensity exercise training has broad beneficial effects on platelet activation markers, paralleled and possibly associated with changes in the lipoprotein profile and in markers of lipid peroxidation and AGE/RAGE axis. Our findings may help explaining why a similar amount of exercise exerts significant benefits in preventing cardiovascular events.

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