{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:04:28Z","timestamp":1781712268038,"version":"3.54.5"},"reference-count":69,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Ectonucleotidases maintain vascular homeostasis by metabolizing extracellular nucleotides, modulating inflammation and thrombosis, and potentially, myocardial flow through adenosine generation. Evidence implicates dysfunction or deficiency of ectonucleotidases CD39 or CD73 in human disease; the utility of measuring levels of circulating ectonucleotidases as plasma biomarkers of coronary artery dysfunction or disease has not been previously reported.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              A total of 529 individuals undergoing clinically indicated positron emission tomography stress testing between 2015 and 2019 were enrolled in this single\u2010center retrospective analysis. Baseline demographics, clinical data, nuclear stress test, and coronary artery calcium score variables were collected, as well as a blood sample. CD39 and CD73 levels were assessed as binary (detectable, undetectable) or continuous variables using ELISAs. Plasma CD39 was detectable in 24% of White and 8% of Black study participants (\n              <jats:italic>P<\/jats:italic>\n              =0.02). Of the clinical history variables examined, ectonucleotidase levels were most strongly associated with underlying liver disease and not other traditional coronary artery disease risk factors. Intriguingly, detection of circulating ectonucleotidase was inversely associated with stress myocardial blood flow (2.3\u00b10.8\u2009mL\/min per g versus 2.7\u2009mL\/min per g\u00b11.1 for detectable versus undetectable CD39 levels,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and global myocardial flow reserve (Pearson correlation between myocardial flow reserve and log(CD73) \u22120.19,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). A subanalysis showed these differences held true independent of liver disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Vasodilatory adenosine is the expected product of local ectonucleotidase activity, yet these data support an inverse relationship between plasma ectonucleotidases, stress myocardial blood flow (CD39), and myocardial flow reserve (CD73). These findings support the conclusion that plasma levels of ectonucleotidases, which may be shed from the endothelial surface, contribute to reduced stress myocardial blood flow and myocardial flow reserve.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027920","type":"journal-article","created":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T10:56:10Z","timestamp":1682765770000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Circulating Ectonucleotidases Signal Impaired Myocardial Perfusion at Rest and Stress"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0401-3904","authenticated-orcid":false,"given":"Rachel G.","family":"Kroll","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine Michigan Medicine Ann Arbor MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6756-3524","authenticated-orcid":false,"given":"Corey","family":"Powell","sequence":"additional","affiliation":[{"name":"Consulting for Statistics, Computing, and Analytics Research University of Michigan Ann Arbor MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine Michigan Medicine Ann Arbor MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha T.","family":"Snider","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of North Carolina at Chapel Hill Chapel Hill NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1871-6915","authenticated-orcid":false,"given":"Cynthia","family":"St. Hilaire","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Departments of Medicine and Bioengineering Vascular Medicine Institute, University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9000-9890","authenticated-orcid":false,"given":"Akshay","family":"Reddy","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine Michigan Medicine Ann Arbor MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine Michigan Medicine Ann Arbor MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Pinsky","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine Michigan Medicine Ann Arbor MI"},{"name":"Department of Molecular &amp; Integrative Physiology University of Michigan Ann Arbor MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7901-1321","authenticated-orcid":false,"given":"Venkatesh L.","family":"Murthy","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine Michigan Medicine Ann Arbor MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0968-3085","authenticated-orcid":false,"given":"Nadia R.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine Michigan Medicine Ann Arbor MI"},{"name":"Division of Cardiovascular Medicine, Department of Medicine Vanderbilt University Medical Center Nashville TN"},{"name":"Department of Biomedical Engineering Vanderbilt University Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36433"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-016-9545-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.2.421"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003671"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.82.5.1595"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.313002"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.89504"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912923"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.313765"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1221"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.023301"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-014-0425-1"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600344R"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal1669"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000571"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-62702-5.00018-4"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1910972116"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01729"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-234625"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12350-021-02775-8"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(90)90282-T"},{"key":"e_1_3_2_24_2","unstructured":"National Kidney Foundation MDRD Study Equation . 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