TY - JOUR

T1 - High-intensity exercise training improves basal platelet prostacyclin sensitivity and potentiates the response to dual anti-platelet therapy in postmenopausal women

AU - Wickham, Kate

AU - Nørregaard, Line Boel

AU - Slingsby, Martina Helena Lundberg

AU - Cheung, Stephen S

AU - Hellsten, Ylva

N1 - CURIS 2022 NEXS 257

PY - 2022

Y1 - 2022

N2 - The risk of thrombotic events dramatically increases with age and may be accelerated in women by the cessation of endogenous estrogen production at menopause. Patients at risk of thrombosis are prescribed dual anti-platelet therapy (DAPT; aspirin and a P2Y12 antagonist) and are encouraged to participate in regular physical activity, as these modalities improve nitric oxideand prostacyclin-mediated inhibition of platelet aggregation. Methods: We assessed prostacyclin sensitivity as well as basal platelet reactivity with and without in vitro DAPT before and after an 8-week high-intensity exercise training program in 13 healthy, sedentary postmenopausal women.The training intervention consisted of three 1 h sessions per week. Isolated platelets were analyzed for thromboxane A2 receptor, thromboxane A2  synthase, cyclooxygenase-1, and prostacyclin receptor protein expression. Additionally, plasma 6-keto prostaglandin F1α and thromboxane B2 levels weredetermined. Results: Exercise training made platelets more sensitive to the inhibitory effects of prostacyclin on thromboxane-, collagen-, and adenosine 5′-diphosphate (ADP)-induced aggregation, as well as thrombin-receptor activator peptide 6- and ADP-induced aggregation with DAPT. However, there was no change in protein expression from isolated platelets or plasma thromboxane B2 andprostacyclin levels following training. Conclusion: Together, these findings emphasize the importance of promoting physical activity as a tool for reducing thrombotic risk in postmenopausal  women and suggest that training status should be considered when prescribing DAPT in this cohort.

AB - The risk of thrombotic events dramatically increases with age and may be accelerated in women by the cessation of endogenous estrogen production at menopause. Patients at risk of thrombosis are prescribed dual anti-platelet therapy (DAPT; aspirin and a P2Y12 antagonist) and are encouraged to participate in regular physical activity, as these modalities improve nitric oxideand prostacyclin-mediated inhibition of platelet aggregation. Methods: We assessed prostacyclin sensitivity as well as basal platelet reactivity with and without in vitro DAPT before and after an 8-week high-intensity exercise training program in 13 healthy, sedentary postmenopausal women.The training intervention consisted of three 1 h sessions per week. Isolated platelets were analyzed for thromboxane A2 receptor, thromboxane A2  synthase, cyclooxygenase-1, and prostacyclin receptor protein expression. Additionally, plasma 6-keto prostaglandin F1α and thromboxane B2 levels weredetermined. Results: Exercise training made platelets more sensitive to the inhibitory effects of prostacyclin on thromboxane-, collagen-, and adenosine 5′-diphosphate (ADP)-induced aggregation, as well as thrombin-receptor activator peptide 6- and ADP-induced aggregation with DAPT. However, there was no change in protein expression from isolated platelets or plasma thromboxane B2 andprostacyclin levels following training. Conclusion: Together, these findings emphasize the importance of promoting physical activity as a tool for reducing thrombotic risk in postmenopausal  women and suggest that training status should be considered when prescribing DAPT in this cohort.

KW - Faculty of Science

KW - Dual anti-platelet therapy

KW - Exercise

KW - Menopause

KW - Platelets

KW - Coagulation

KW - Thrombosis

KW - Prostacyclin

U2 - 10.3390/biom12101501

DO - 10.3390/biom12101501

M3 - Journal article

C2 - 36291709

VL - 12

JO - Biomolecules

JF - Biomolecules

SN - 2218-273X

IS - 10

M1 - 1501

ER -