Juho Jalkanen1, Gennady G Yegutkin1, Maija Hollmén1, Kristiina Aalto1, Tuomas Kiviniemi1, Veikko Salomaa1, Sirpa Jalkanen2, Harri Hakovirta1. 1. From the Department of Vascular Surgery (J.J., H.H.) and Heart Center (T.K.), Turku University Hospital, Turku, Finland; Medicity Research Laboratory, Department of Microbiology and Immunology, University of Turku, Turku, Finland (G.G.Y., M.H., K.A., S.J.); and National Institute for Health and Welfare, Helsinki, Finland (V.S.). 2. From the Department of Vascular Surgery (J.J., H.H.) and Heart Center (T.K.), Turku University Hospital, Turku, Finland; Medicity Research Laboratory, Department of Microbiology and Immunology, University of Turku, Turku, Finland (G.G.Y., M.H., K.A., S.J.); and National Institute for Health and Welfare, Helsinki, Finland (V.S.). sirpa.jalkanen@utu.fi.
Abstract
RATIONALE: Purinergic signaling plays an important role in inflammation and vascular integrity, but little is known about purinergic mechanisms during the pathogenesis of atherosclerosis in humans. OBJECTIVE: The objective of this study is to study markers of purinergic signaling in a cohort of patients with peripheral artery disease. METHODS AND RESULTS: Plasma ATP and ADP levels and serum nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39) and ecto-5'-nucleotidase/CD73 activities were measured in 226 patients with stable peripheral artery disease admitted for nonurgent invasive imaging and treatment. The major findings were that ATP, ADP, and CD73 values were higher in atherosclerotic patients than in controls without clinically evident peripheral artery disease (P<0.0001). Low CD39 activity was associated with disease progression (P=0.01). In multivariable linear regression models, high CD73 activity was associated with chronic hypoxia (P=0.001). Statin use was associated with lower ADP (P=0.041) and tended to associate with higher CD73 (P=0.054), while lower ATP was associated with the use of angiotensin receptor blockers (P=0.015). CONCLUSIONS: Purinergic signaling plays an important role in peripheral artery disease progression. Elevated levels of circulating ATP and ADP are especially associated with atherosclerotic diseases of younger age and smoking. The antithrombotic and anti-inflammatory effects of statins may partly be explained by their ability to lower ADP. We suggest that the prothrombotic nature of smoking could be a cause of elevated ADP, and this may explain why cardiovascular patients who smoke benefit from platelet P2Y12 receptor antagonists more than their nonsmoking peers.
RATIONALE: Purinergic signaling plays an important role in inflammation and vascular integrity, but little is known about purinergic mechanisms during the pathogenesis of atherosclerosis in humans. OBJECTIVE: The objective of this study is to study markers of purinergic signaling in a cohort of patients with peripheral artery disease. METHODS AND RESULTS: Plasma ATP and ADP levels and serum nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39) and ecto-5'-nucleotidase/CD73 activities were measured in 226 patients with stable peripheral artery disease admitted for nonurgent invasive imaging and treatment. The major findings were that ATP, ADP, and CD73 values were higher in atheroscleroticpatients than in controls without clinically evident peripheral artery disease (P<0.0001). Low CD39 activity was associated with disease progression (P=0.01). In multivariable linear regression models, high CD73 activity was associated with chronic hypoxia (P=0.001). Statin use was associated with lower ADP (P=0.041) and tended to associate with higher CD73 (P=0.054), while lower ATP was associated with the use of angiotensin receptor blockers (P=0.015). CONCLUSIONS: Purinergic signaling plays an important role in peripheral artery disease progression. Elevated levels of circulating ATP and ADP are especially associated with atherosclerotic diseases of younger age and smoking. The antithrombotic and anti-inflammatory effects of statins may partly be explained by their ability to lower ADP. We suggest that the prothrombotic nature of smoking could be a cause of elevated ADP, and this may explain why cardiovascular patients who smoke benefit from platelet P2Y12 receptor antagonists more than their nonsmoking peers.
Authors: Roman Covarrubias; Elena Chepurko; Adam Reynolds; Zachary M Huttinger; Ryan Huttinger; Katherine Stanfill; Debra G Wheeler; Tatiana Novitskaya; Simon C Robson; Karen M Dwyer; Peter J Cowan; Richard J Gumina Journal: Arterioscler Thromb Vasc Biol Date: 2016-07-14 Impact factor: 8.311
Authors: Nadia R Sutton; Diane Bouïs; Kris M Mann; Imran M Rashid; Alexandra L McCubbrey; Matt C Hyman; Daniel R Goldstein; Annie Mei; David J Pinsky Journal: Arterioscler Thromb Vasc Biol Date: 2019-10-17 Impact factor: 8.311
Authors: Charlotte Roy; Julie Tabiasco; Antoine Caillon; Yves Delneste; Jean Merot; Julie Favre; Anne Laure Guihot; Ludovic Martin; Daniele C Nascimento; Bernhard Ryffel; Simon C Robson; Jean Sévigny; Daniel Henrion; Gilles Kauffenstein Journal: Purinergic Signal Date: 2017-12-13 Impact factor: 3.765