{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:39:43Z","timestamp":1778837983586,"version":"3.51.4"},"reference-count":60,"publisher":"SAGE Publications","issue":"4-6","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>The objective of this study is to identify mechanisms for adipose stromal vascular fraction's (SVF) restorative effects on vasodilation in aging-induced coronary microvascular disease (CMD). We hypothesize that reactive oxygen species (ROS) diminish \u03b21-adrenergic receptor (\u03b21ADR)- and flow-mediated dilation (FMD) in coronary arterioles, reversible by SVF and adipose-derived stem cells (ADSCs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>SVF attenuates aging-induced chronic accumulation of ROS and pro-oxidant gene and protein expression with enhancement of antioxidant gene and protein expression and glutathione, but not nitric oxide. ADSCs attenuate hydrogen peroxide while restoring nitric oxide and glutathione. Mass spectrometry of SVF- and ADSC-conditioned media reveals abundant antioxidant proteins suggesting a paracrine mechanism. FMD and \u03b21ADR-mediated dilation diminished with aging, restored with SVF and ADSCs. FMD was restored by a switch in the acute signaling mediator from hydrogen peroxide in aging to peroxynitrite with SVF and ADSCs. Vasorelaxation to \u03b21ADR-agonism was mechanistically linked with hydrogen peroxide, nitric oxide, and glutathione. Exogenous ROS eliminates isoproterenol-mediated dilation in youth that is blocked by inhibition of pro-desensitization and internalization proteins while nitric oxide enhances isoproterenol-mediated dilation in aging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>We introduce a novel mechanism by which ROS impacts \u03b21ADR trafficking: the ROS\/RNS-\u03b21ADR desensitization and internalization axis. Aging-induced ROS shunts \u03b21ADR from the plasma membrane into endosomes. SVF reduces oxidative burden, restoring functional \u03b21ADR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      SVF (and ADSCs to a lesser extent) reduce oxidative stress, and restore flow- and \u03b21ADR-mediated vasodilation in aging. SVF represents a promising therapeutic strategy for CMD by addressing root cause of pathology; that is, oxidative stress-mediated hyperconstriction.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                      . 38, 261\u2013281.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2021.0249","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T06:37:19Z","timestamp":1660199839000},"page":"261-281","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Stromal Vascular Fraction Restores Vasodilatory Function by Reducing Oxidative Stress in Aging-Induced Coronary Microvascular Disease"],"prefix":"10.1177","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6689-0216","authenticated-orcid":false,"given":"Evan Paul","family":"Tracy","sequence":"first","affiliation":[{"name":"Department of Physiology and University of Louisville, Louisville, Kentucky, USA."},{"name":"Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5195-2840","authenticated-orcid":false,"given":"Michaela","family":"Dukes","sequence":"additional","affiliation":[{"name":"Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7686-7880","authenticated-orcid":false,"given":"Gabrielle","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Physiology and University of Louisville, Louisville, Kentucky, USA."},{"name":"Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-1223","authenticated-orcid":false,"given":"Jason E.","family":"Beare","sequence":"additional","affiliation":[{"name":"Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, USA."},{"name":"Kentucky Spinal Cord Injury Research Center and University of Louisville, Louisville, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4338-0456","authenticated-orcid":false,"given":"Rajeev","family":"Nair","sequence":"additional","affiliation":[{"name":"Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2507-1203","authenticated-orcid":false,"given":"Amanda Jo","family":"LeBlanc","sequence":"additional","affiliation":[{"name":"Cardiovascular Innovation Institute, University of Louisville, Louisville, Kentucky, USA."},{"name":"Department of Cardiovascular and Thoracic Surgery, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"e_1_3_7_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00164.2018"},{"key":"e_1_3_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2015.01.044"},{"key":"e_1_3_7_4_1","first-page":"947","volume":"8","author":"Alexander R.","year":"2016","unstructured":"Alexander R. Understanding mechanical emulsification (Nanofat) versus enzymatic isolation of tissue stromal vascular fraction (tSVF) cells from adipose tissue: Potential uses in biocellular regenerative medicine. J Prolother, 2016; 8:947\u2013960.","journal-title":"J Prolother"},{"key":"e_1_3_7_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7169275"},{"key":"e_1_3_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307918"},{"key":"e_1_3_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-016-0594-x"},{"key":"e_1_3_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)90305-0"},{"key":"e_1_3_7_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1986.251.4.H779"},{"issue":"1","key":"e_1_3_7_10_1","first-page":"131","article-title":"Positive inotropic\/vasodilator agents","volume":"7","author":"Colucci WS","year":"1989","unstructured":"Colucci WS. Positive inotropic\/vasodilator agents. Cardiol Clin, 1989; 7(1):131\u2013144. PMID: 2565161.","journal-title":"Cardiol Clin"},{"key":"e_1_3_7_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.88.1.62"},{"key":"e_1_3_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-15458-5_19"},{"key":"e_1_3_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja802355u"},{"key":"e_1_3_7_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000269183.13937.e8"},{"key":"e_1_3_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2014.02.007"},{"key":"e_1_3_7_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00365.2017"},{"key":"e_1_3_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12649"},{"key":"e_1_3_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.05.031"},{"key":"e_1_3_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-014-1952-3"},{"key":"e_1_3_7_20_1","doi-asserted-by":"publisher","DOI":"10.2220\/biomedres.31.293"},{"key":"e_1_3_7_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1358863X14537546"},{"key":"e_1_3_7_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.07802"},{"key":"e_1_3_7_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1989.256.1.H66"},{"key":"e_1_3_7_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00058.2018"},{"key":"e_1_3_7_25_1","doi-asserted-by":"publisher","DOI":"10.4174\/astr.2019.97.4.159"},{"key":"e_1_3_7_26_1","doi-asserted-by":"crossref","unstructured":"Katunaric B SenthilKumar G Schultz ME et al. Role of NOX2 in ceramide-induced human microvascular endothelial dysfunction. J Fed Am Soc Exp Biol 2022; 36(S1); doi: https:\/\/doi.org\/10.1096\/fasebj.2022.36.S1.R4005.","DOI":"10.1096\/fasebj.2022.36.S1.R4005"},{"key":"e_1_3_7_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0202934"},{"key":"e_1_3_7_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11040467"},{"key":"e_1_3_7_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00735.2011"},{"key":"e_1_3_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101727"},{"key":"e_1_3_7_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000181717.87204.2f"},{"key":"e_1_3_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.06.027"},{"key":"e_1_3_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.04.061"},{"key":"e_1_3_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-019-0159-5"},{"key":"e_1_3_7_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi971894b"},{"key":"e_1_3_7_36_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20190177"},{"key":"e_1_3_7_37_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0235"},{"key":"e_1_3_7_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1995.1006"},{"key":"e_1_3_7_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00497"},{"key":"e_1_3_7_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.REV119.006136"},{"key":"e_1_3_7_41_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2014-0252"},{"key":"e_1_3_7_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1549-8719.2011.00139.x"},{"key":"e_1_3_7_43_1","unstructured":"National Research Council. Guide for the Care and Use of Laboratory Animals. (8th ed.) Washington DC; National Academies Press; 2011."},{"key":"e_1_3_7_44_1","unstructured":"Probes for Mitochondria. In: Molecular Probes Handbook A Guide to Fluorescent Probes and Labeling Technologies. (Johnson I Spence MTZ eds.) Carlsbad CA: Life Technologies; 2010."},{"key":"e_1_3_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59983-4"},{"key":"e_1_3_7_46_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2005.7.619"},{"key":"e_1_3_7_47_1","doi-asserted-by":"publisher","DOI":"10.1159\/000526002"},{"key":"e_1_3_7_48_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102069"},{"key":"e_1_3_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-021-00455-6"},{"key":"e_1_3_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1568-s1637(02)00063-6"},{"key":"e_1_3_7_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33592-8"},{"key":"e_1_3_7_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu313"},{"key":"e_1_3_7_53_1","doi-asserted-by":"publisher","DOI":"10.1159\/000438594"},{"key":"e_1_3_7_54_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2021.0031"},{"key":"e_1_3_7_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00674.2021"},{"key":"e_1_3_7_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja061972v"},{"key":"e_1_3_7_57_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.21.18042"},{"key":"e_1_3_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.02.025"},{"key":"e_1_3_7_59_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.6221"},{"key":"e_1_3_7_60_1","doi-asserted-by":"publisher","DOI":"10.2310\/JIM.0b013e318180a91f"},{"key":"e_1_3_7_61_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546519848678"}],"container-title":["Antioxidants &amp; Redox Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2021.0249","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/ars.2021.0249","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2021.0249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:55:17Z","timestamp":1777377317000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/ars.2021.0249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2]]},"references-count":60,"journal-issue":{"issue":"4-6","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1089\/ars.2021.0249"],"URL":"https:\/\/doi.org\/10.1089\/ars.2021.0249","relation":{},"ISSN":["1523-0864","1557-7716"],"issn-type":[{"value":"1523-0864","type":"print"},{"value":"1557-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2]]}}}