Adipose-derived cells improve left ventricular diastolic function and increase microvascular perfusion in advanced age
An early manifestation of coronary artery disease in advanced age is the development of microvascular dysfunction leading to deficits in diastolic function. Our lab has previously shown that epicardial treatment with adipose-derived stromal vascular fraction (SVF) preserves microvascular function fo...
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| description | An early manifestation of coronary artery disease in advanced age is the development of microvascular dysfunction leading to deficits in diastolic function. Our lab has previously shown that epicardial treatment with adipose-derived stromal vascular fraction (SVF) preserves microvascular function following coronary ischemia in a young rodent model. Follow-up studies showed intravenous (i.v.) delivery of SVF allows the cells to migrate to the walls of small vessels and reset vasomotor tone. Therefore we tested the hypothesis that the i.v. cell injection of SVF would reverse the coronary microvascular dysfunction associated with aging in a rodent model. Fischer 344 rats were divided into 4 groups: young control (YC), old control (OC), old + rat aortic endothelial cells (O+EC) and old + GFP+ SVF cells (O+SVF). After four weeks, cardiac function and coronary flow reserve (CFR) were measured via echocardiography, and hearts were explanted either for histology or isolation of coronary arterioles for vessel reactivity studies. In a subgroup of animals, microspheres were injected during resting and dobutamine-stimulated conditions to measure coronary blood flow. GFP+ SVF cells engrafted and persisted in the myocardium and coronary vasculature four weeks following i.v. injection. Echocardiography showed age-related diastolic dysfunction without accompanying systolic dysfunction; diastolic function was improved in old rats after SVF treatment. Ultrasound and microsphere data both showed increased stimulated coronary blood flow in O+SVF rats compared to OC and O+EC, while isolated vessel reactivity was mostly unchanged. I.v.-injected SVF cells were capable of incorporating into the vasculature of the aging heart and are shown in this study to improve CFR and diastolic function in a model of advanced age. Importantly, SVF injection did not lead to arrhythmias or increased mortality in aged rats. SVF cells provide an autologous cell therapy option for treatment of microvascular and cardiac dysfunction in aged populations. |
| doi_str_mv | 10.1371/journal.pone.0202934 |
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Our lab has previously shown that epicardial treatment with adipose-derived stromal vascular fraction (SVF) preserves microvascular function following coronary ischemia in a young rodent model. Follow-up studies showed intravenous (i.v.) delivery of SVF allows the cells to migrate to the walls of small vessels and reset vasomotor tone. Therefore we tested the hypothesis that the i.v. cell injection of SVF would reverse the coronary microvascular dysfunction associated with aging in a rodent model. Fischer 344 rats were divided into 4 groups: young control (YC), old control (OC), old + rat aortic endothelial cells (O+EC) and old + GFP+ SVF cells (O+SVF). After four weeks, cardiac function and coronary flow reserve (CFR) were measured via echocardiography, and hearts were explanted either for histology or isolation of coronary arterioles for vessel reactivity studies. In a subgroup of animals, microspheres were injected during resting and dobutamine-stimulated conditions to measure coronary blood flow. GFP+ SVF cells engrafted and persisted in the myocardium and coronary vasculature four weeks following i.v. injection. Echocardiography showed age-related diastolic dysfunction without accompanying systolic dysfunction; diastolic function was improved in old rats after SVF treatment. Ultrasound and microsphere data both showed increased stimulated coronary blood flow in O+SVF rats compared to OC and O+EC, while isolated vessel reactivity was mostly unchanged. I.v.-injected SVF cells were capable of incorporating into the vasculature of the aging heart and are shown in this study to improve CFR and diastolic function in a model of advanced age. Importantly, SVF injection did not lead to arrhythmias or increased mortality in aged rats. SVF cells provide an autologous cell therapy option for treatment of microvascular and cardiac dysfunction in aged populations.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0202934</identifier><identifier>PMID: 30142193</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetylcholine - pharmacology ; Adipocytes - cytology ; Age ; Aging ; Animals ; Aorta ; Arterioles ; Arterioles - drug effects ; Arterioles - physiology ; Biology and Life Sciences ; Blood ; Blood flow ; Blood vessels ; Cardiovascular disease ; Care and treatment ; Cell migration ; Clinical trials ; Coronary artery ; Coronary artery disease ; Coronary Circulation - drug effects ; Coronary heart disease ; Coronary vessels ; Development and progression ; Echocardiography ; Elderly ; Endothelial cells ; Female ; Health aspects ; Heart ; Heart failure ; Histology ; Injection ; Intravenous administration ; Ischemia ; Kinases ; Laboratory animals ; Medicine and Health Sciences ; Microspheres ; Microvasculature ; Myocardium ; Nitroprusside - pharmacology ; Perfusion ; Physical Sciences ; Physiology ; Rats ; Research and Analysis Methods ; Risk factors ; Rodents ; Stem cells ; Stromal Cells - cytology ; Subgroups ; Ultrasound ; Ventricle ; Ventricular Function, Left - drug effects ; Women</subject><ispartof>PloS one, 2018-08, Vol.13 (8), p.e0202934-e0202934</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Kelm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Kelm et al 2018 Kelm et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-405209c368a56d058095fd1ac352fbfe2202a29076fd9a8f27193a33d948a7443</citedby><cites>FETCH-LOGICAL-c692t-405209c368a56d058095fd1ac352fbfe2202a29076fd9a8f27193a33d948a7443</cites><orcidid>0000-0002-9147-6842 ; 0000-0003-3988-1223 ; 0000-0002-8854-6045</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108481/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108481/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30142193$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Peterson, Jonathan M.</contributor><creatorcontrib>Kelm, Natia Q</creatorcontrib><creatorcontrib>Beare, Jason E</creatorcontrib><creatorcontrib>Yuan, Fangping</creatorcontrib><creatorcontrib>George, Monika</creatorcontrib><creatorcontrib>Shofner, Charles M</creatorcontrib><creatorcontrib>Keller, Bradley B</creatorcontrib><creatorcontrib>Hoying, James B</creatorcontrib><creatorcontrib>LeBlanc, Amanda J</creatorcontrib><title>Adipose-derived cells improve left ventricular diastolic function and increase microvascular perfusion in advanced age</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>An early manifestation of coronary artery disease in advanced age is the development of microvascular dysfunction leading to deficits in diastolic function. Our lab has previously shown that epicardial treatment with adipose-derived stromal vascular fraction (SVF) preserves microvascular function following coronary ischemia in a young rodent model. Follow-up studies showed intravenous (i.v.) delivery of SVF allows the cells to migrate to the walls of small vessels and reset vasomotor tone. Therefore we tested the hypothesis that the i.v. cell injection of SVF would reverse the coronary microvascular dysfunction associated with aging in a rodent model. Fischer 344 rats were divided into 4 groups: young control (YC), old control (OC), old + rat aortic endothelial cells (O+EC) and old + GFP+ SVF cells (O+SVF). After four weeks, cardiac function and coronary flow reserve (CFR) were measured via echocardiography, and hearts were explanted either for histology or isolation of coronary arterioles for vessel reactivity studies. 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SVF cells provide an autologous cell therapy option for treatment of microvascular and cardiac dysfunction in aged populations.</description><subject>Acetylcholine - pharmacology</subject><subject>Adipocytes - cytology</subject><subject>Age</subject><subject>Aging</subject><subject>Animals</subject><subject>Aorta</subject><subject>Arterioles</subject><subject>Arterioles - drug effects</subject><subject>Arterioles - physiology</subject><subject>Biology and Life Sciences</subject><subject>Blood</subject><subject>Blood flow</subject><subject>Blood vessels</subject><subject>Cardiovascular disease</subject><subject>Care and treatment</subject><subject>Cell migration</subject><subject>Clinical trials</subject><subject>Coronary artery</subject><subject>Coronary artery disease</subject><subject>Coronary Circulation - drug effects</subject><subject>Coronary heart disease</subject><subject>Coronary vessels</subject><subject>Development and progression</subject><subject>Echocardiography</subject><subject>Elderly</subject><subject>Endothelial cells</subject><subject>Female</subject><subject>Health aspects</subject><subject>Heart</subject><subject>Heart failure</subject><subject>Histology</subject><subject>Injection</subject><subject>Intravenous administration</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Medicine and Health Sciences</subject><subject>Microspheres</subject><subject>Microvasculature</subject><subject>Myocardium</subject><subject>Nitroprusside - pharmacology</subject><subject>Perfusion</subject><subject>Physical Sciences</subject><subject>Physiology</subject><subject>Rats</subject><subject>Research and Analysis Methods</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Stem cells</subject><subject>Stromal Cells - cytology</subject><subject>Subgroups</subject><subject>Ultrasound</subject><subject>Ventricle</subject><subject>Ventricular Function, Left - drug effects</subject><subject>Women</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9uK2zAQhk1p6R7aNyitobC0F0l1smPdFMLSQ2BhoadbMdEhUVAsr2Sb9u0rJ94lLntRfGEjffOP55-ZLHuF0RzTBf6w812owc0bX-s5Iohwyp5k55hTMisJok9Pvs-yixh3CBW0Ksvn2RlFmJF0e571S2UbH_VM6WB7rXKpnYu53TfB9zp32rR5r-s2WNk5CLmyEFvvrMxNV8vW-jqHWuW2lkFD1PneyhQI8Ug3OpguDpBNnOqhlikFbPSL7JkBF_XL8X2Z_fz86cf119nN7ZfV9fJmJktO2hlDBUFc0rKColSoqBAvjMIgaUHM2miSygbC0aI0ikNlyCIVBZQqzipYMEYvszdH3cb5KEbLokiipKIck4FYHQnlYSeaYPcQ_ggPVhwOfNgICK2VTosS8TUDpolSiCmz5ogspJKKVZxXWEHS-jhm69Z7reTgG7iJ6PSmtlux8b0oMapYhZPAu1Eg-LtOx1bsbRw6ArX23eG_KUOE0CKhb_9BH69upDaQCrC18SmvHETFsihwiRk9uDR_hEqP0qmfab6MTeeTgPeTgMS0-ne7gS5Gsfr-7f_Z219T9uqE3Wpw7TZ61w1zFqcgO4Jp2mIM2jyYjJEY1uPeDTGshxjXI4W9Pm3QQ9D9PtC_VmgLXA</recordid><startdate>20180824</startdate><enddate>20180824</enddate><creator>Kelm, Natia Q</creator><creator>Beare, Jason E</creator><creator>Yuan, Fangping</creator><creator>George, Monika</creator><creator>Shofner, Charles M</creator><creator>Keller, Bradley B</creator><creator>Hoying, James B</creator><creator>LeBlanc, Amanda J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-9147-6842</orcidid><orcidid>https://orcid.org/0000-0003-3988-1223</orcidid><orcidid>https://orcid.org/0000-0002-8854-6045</orcidid></search><sort><creationdate>20180824</creationdate><title>Adipose-derived cells improve left ventricular diastolic function and increase microvascular perfusion in advanced age</title><author>Kelm, Natia Q ; Beare, Jason E ; Yuan, Fangping ; George, Monika ; Shofner, Charles M ; Keller, Bradley B ; Hoying, James B ; LeBlanc, Amanda J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-405209c368a56d058095fd1ac352fbfe2202a29076fd9a8f27193a33d948a7443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Acetylcholine - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kelm, Natia Q</au><au>Beare, Jason E</au><au>Yuan, Fangping</au><au>George, Monika</au><au>Shofner, Charles M</au><au>Keller, Bradley B</au><au>Hoying, James B</au><au>LeBlanc, Amanda J</au><au>Peterson, Jonathan M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipose-derived cells improve left ventricular diastolic function and increase microvascular perfusion in advanced age</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-08-24</date><risdate>2018</risdate><volume>13</volume><issue>8</issue><spage>e0202934</spage><epage>e0202934</epage><pages>e0202934-e0202934</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>An early manifestation of coronary artery disease in advanced age is the development of microvascular dysfunction leading to deficits in diastolic function. Our lab has previously shown that epicardial treatment with adipose-derived stromal vascular fraction (SVF) preserves microvascular function following coronary ischemia in a young rodent model. Follow-up studies showed intravenous (i.v.) delivery of SVF allows the cells to migrate to the walls of small vessels and reset vasomotor tone. Therefore we tested the hypothesis that the i.v. cell injection of SVF would reverse the coronary microvascular dysfunction associated with aging in a rodent model. Fischer 344 rats were divided into 4 groups: young control (YC), old control (OC), old + rat aortic endothelial cells (O+EC) and old + GFP+ SVF cells (O+SVF). After four weeks, cardiac function and coronary flow reserve (CFR) were measured via echocardiography, and hearts were explanted either for histology or isolation of coronary arterioles for vessel reactivity studies. In a subgroup of animals, microspheres were injected during resting and dobutamine-stimulated conditions to measure coronary blood flow. GFP+ SVF cells engrafted and persisted in the myocardium and coronary vasculature four weeks following i.v. injection. Echocardiography showed age-related diastolic dysfunction without accompanying systolic dysfunction; diastolic function was improved in old rats after SVF treatment. Ultrasound and microsphere data both showed increased stimulated coronary blood flow in O+SVF rats compared to OC and O+EC, while isolated vessel reactivity was mostly unchanged. I.v.-injected SVF cells were capable of incorporating into the vasculature of the aging heart and are shown in this study to improve CFR and diastolic function in a model of advanced age. Importantly, SVF injection did not lead to arrhythmias or increased mortality in aged rats. SVF cells provide an autologous cell therapy option for treatment of microvascular and cardiac dysfunction in aged populations.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30142193</pmid><doi>10.1371/journal.pone.0202934</doi><tpages>e0202934</tpages><orcidid>https://orcid.org/0000-0002-9147-6842</orcidid><orcidid>https://orcid.org/0000-0003-3988-1223</orcidid><orcidid>https://orcid.org/0000-0002-8854-6045</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_2092839124 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acetylcholine - pharmacology Adipocytes - cytology Age Aging Animals Aorta Arterioles Arterioles - drug effects Arterioles - physiology Biology and Life Sciences Blood Blood flow Blood vessels Cardiovascular disease Care and treatment Cell migration Clinical trials Coronary artery Coronary artery disease Coronary Circulation - drug effects Coronary heart disease Coronary vessels Development and progression Echocardiography Elderly Endothelial cells Female Health aspects Heart Heart failure Histology Injection Intravenous administration Ischemia Kinases Laboratory animals Medicine and Health Sciences Microspheres Microvasculature Myocardium Nitroprusside - pharmacology Perfusion Physical Sciences Physiology Rats Research and Analysis Methods Risk factors Rodents Stem cells Stromal Cells - cytology Subgroups Ultrasound Ventricle Ventricular Function, Left - drug effects Women |
| title | Adipose-derived cells improve left ventricular diastolic function and increase microvascular perfusion in advanced age |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T23%3A49%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Adipose-derived%20cells%20improve%20left%20ventricular%20diastolic%20function%20and%20increase%20microvascular%20perfusion%20in%20advanced%20age&rft.jtitle=PloS%20one&rft.au=Kelm,%20Natia%20Q&rft.date=2018-08-24&rft.volume=13&rft.issue=8&rft.spage=e0202934&rft.epage=e0202934&rft.pages=e0202934-e0202934&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0202934&rft_dat=%3Cgale_plos_%3EA551614344%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2092839124&rft_id=info:pmid/30142193&rft_galeid=A551614344&rft_doaj_id=oai_doaj_org_article_609b4a4e2dd04dfb9027cdcd489981da&rfr_iscdi=true |