{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T03:45:47Z","timestamp":1794109547812,"version":"4.8.0"},"reference-count":77,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["HL142710"],"award-info":[{"award-number":["HL142710"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["GM103492"],"award-info":[{"award-number":["GM103492"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["16SDG27260070"],"award-info":[{"award-number":["16SDG27260070"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Louisville School of Medicine"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2021,3,19]]},"abstract":"<jats:sec>\n            <jats:title>Rationale:<\/jats:title>\n            <jats:p>Voltage-gated potassium (Kv) channels in vascular smooth muscle are essential for coupling myocardial blood flow (MBF) with the metabolic demand of the heart. These channels consist of a transmembrane pore domain that associates with auxiliary Kv\u03b2 (voltage-gated potassium channel \u03b2)1 and Kv\u03b22 proteins, which differentially regulate Kv function in excitable cells. Nonetheless, the physiological role of Kv\u03b2 proteins in regulating vascular tone and metabolic hyperemia in the heart remains unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>To test the hypothesis that Kv\u03b2 proteins confer oxygen sensitivity to vascular tone and are required for regulating blood flow in the heart.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              Mice lacking Kv\u03b22 subunits exhibited suppressed MBF, impaired cardiac contractile performance, and failed to maintain elevated arterial blood pressure in response to catecholamine-induced stress. In contrast, ablation of Kv\u03b21.1 reduced cardiac workload, modestly elevated MBF, and preserved cardiac function during stress compared with wild-type mice. Coronary arteries isolated from Kv\u03b22\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              , but not Kv\u03b21.1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              , mice had severely blunted vasodilation to hypoxia when compared with arteries from wild-type mice. Moreover, vasodilation of small diameter coronary and mesenteric arteries due to L-lactate, a biochemical marker of reduced tissue oxygenation and anaerobic metabolism, was significantly attenuated in vessels isolated from Kv\u03b22\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. Inducible enhancement of the Kv\u03b21:Kv\u03b22 ratio in Kv1 channels of arterial smooth muscle abolished L-lactate-induced vasodilation and suppressed the relationship between MBF and cardiac workload.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>The Kv\u03b2 proteins differentially regulate vascular tone and MBF, whereby Kv\u03b22 promotes, and Kv\u03b21.1 inhibits oxygen-dependent vasodilation and augments blood flow upon heightened metabolic demand.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.120.317715","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T10:00:33Z","timestamp":1611741633000},"page":"738-751","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Myocardial Blood Flow Control by Oxygen Sensing Vascular Kv\u03b2 Proteins"],"prefix":"10.1161","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1188-6746","authenticated-orcid":true,"given":"Vahagn","family":"Ohanyan","sequence":"first","affiliation":[{"name":"Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown (V.O., T.P., G.M., W.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"Raph","sequence":"additional","affiliation":[{"name":"Division of Environmental Medicine, Department of Medicine, Diabetes and Obesity Center, University of Louisville, KY (S.M.R., M.M.D., X.H., J.B.M., A.B., M.A.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6234-5352","authenticated-orcid":true,"given":"Marc M.","family":"Dwenger","sequence":"additional","affiliation":[{"name":"Division of Environmental Medicine, Department of Medicine, Diabetes and Obesity Center, University of Louisville, KY (S.M.R., M.M.D., X.H., J.B.M., A.B., M.A.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Environmental Medicine, Department of Medicine, Diabetes and Obesity Center, University of Louisville, KY (S.M.R., M.M.D., X.H., J.B.M., A.B., M.A.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Pucci","sequence":"additional","affiliation":[{"name":"Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown (V.O., T.P., G.M., W.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown (V.O., T.P., G.M., W.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"IV","given":"Joseph B.","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Environmental Medicine, Department of Medicine, Diabetes and Obesity Center, University of Louisville, KY (S.M.R., M.M.D., X.H., J.B.M., A.B., M.A.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4522-7914","authenticated-orcid":true,"given":"William M.","family":"Chilian","sequence":"additional","affiliation":[{"name":"Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown (V.O., T.P., G.M., W.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruni","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Division of Environmental Medicine, Department of Medicine, Diabetes and Obesity Center, University of Louisville, KY (S.M.R., M.M.D., X.H., J.B.M., A.B., M.A.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8872-158X","authenticated-orcid":true,"given":"Matthew A.","family":"Nystoriak","sequence":"additional","affiliation":[{"name":"Division of Environmental Medicine, Department of Medicine, Diabetes and Obesity Center, University of Louisville, KY (S.M.R., M.M.D., X.H., J.B.M., A.B., M.A.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000757"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.05.064"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198811173192002"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.110.082883"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2005.067934"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.01.054"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0735-1097(99)00082-0"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1983.63.1.1"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c160016"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.29.3.422"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12334"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306642"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-016-0575-0"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008259200"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00354.2004"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.247940"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00020.2009"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2019.09.013"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12431"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2017.03.011"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12426"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12424"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.4.H1351"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1080\/10739680802461950"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.249aa.x"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1006\/mvre.1999.2212"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.37.4.438"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.46.6.771"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/0-306-46825-5_21"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00172.2006"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-012-1093-z"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/369289a0"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034525"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1030514"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013180"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.81.1.349"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaf9647"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00160a018"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000126047.82846.20"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12421"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-015-0715-4"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1995.269.1.H348"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.259.1.C3"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017321"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.2.H448"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2015.1036205"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2010.04.004"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(90)90052-h"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/345535a0"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291x(90)90836-c"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207984200"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.41.25824"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.18.11728"},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-1465"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01003.2006"},{"key":"e_1_3_6_57_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00696.2006"},{"key":"e_1_3_6_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90004-3"},{"key":"e_1_3_6_59_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi800301b"},{"key":"e_1_3_6_60_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513809200"},{"key":"e_1_3_6_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100316108"},{"key":"e_1_3_6_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.05.102"},{"key":"e_1_3_6_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0009-2797(02)00190-4"},{"key":"e_1_3_6_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12418"},{"key":"e_1_3_6_65_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00325.2019"},{"key":"e_1_3_6_66_2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.5.4.257"},{"key":"e_1_3_6_67_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111465200"},{"key":"e_1_3_6_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2003.10.031"},{"key":"e_1_3_6_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0735-1097(97)00029-6"},{"key":"e_1_3_6_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0735-1097(00)00697-5"},{"key":"e_1_3_6_71_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.97.5.473"},{"key":"e_1_3_6_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.11.044"},{"key":"e_1_3_6_73_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc4501.098954"},{"key":"e_1_3_6_74_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.707737"},{"key":"e_1_3_6_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(76)90491-4"},{"key":"e_1_3_6_76_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00710.2011"},{"key":"e_1_3_6_77_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00760.2010"},{"key":"e_1_3_6_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth947"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.120.317715","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T04:33:29Z","timestamp":1715574809000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.120.317715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,19]]},"references-count":77,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,3,19]]}},"alternative-id":["10.1161\/CIRCRESAHA.120.317715"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.120.317715","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,19]]},"assertion":[{"value":"2020-07-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}