title: Effects of high-amount-high-intensity exercise on in vivo platelet activation: modulation by lipid peroxidation and AGE/RAGE axis.
abstract: 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)F(2α) 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-PGF(2α) (21%), plasma P-selectin (27%), CD40L (35%) and a 61% increase in esRAGE were observed. Multiple regression analysis revealed that urinary 8-iso-PGF(2α) [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.
authors.affiliation: Giovanni Davì, Center of Excellence on Aging, "G. D'Annunzio" University Foundation, Via Colle dell'Ara, 66013 Chieti, Italy, Tel.: +39 0871 541312, Fax: +39 0871 541261, E-mail: gdavi@unich.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.forename: Natale
authors.initials: N
authors.lastname: Vazzana
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Iodice
authors.forename: Stefano
authors.initials: S
authors.lastname: Lattanzio
authors.forename: Rossella
authors.initials: R
authors.lastname: Liani
authors.forename: Rosa Grazia
authors.initials: RG
authors.lastname: Bellomo
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Lessiani
authors.forename: Francesca
authors.initials: F
authors.lastname: Perego
authors.forename: Raoul
authors.initials: R
authors.lastname: Saggini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D023201:CD40 Ligand / Q000097:blood; D015444:Exercise / Q000502:physiology; D005260:Female; D017127:Glycation End Products, Advanced; D006801:Humans; D028421:Isoprostanes / Q000652:urine*; D015227:Lipid Peroxidation / Q000502:physiology; D008075:Lipoproteins, HDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000502:physiology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D013931:Thromboxanes / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D028421:Isoprostanes; D008075:Lipoproteins, HDL; D019007:P-Selectin; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013931:Thromboxanes; D023201:CD40 Ligand; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2
keywords: Aerobic exercise; esRAGE; oxidative stress; platelet activation