SarcTrack
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR/Cas9 genome editing provide unparalleled opportunities to study cardiac biology and disease. However, sarcomeres, the fundamental units of myocyte contraction, are immature and nonlinear in hiPSC-CMs, w...
Saved in:
Published in | Circulation research Vol. 124; no. 8; p. 1172 |
---|---|
Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
12.04.2019
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR/Cas9 genome editing provide unparalleled opportunities to study cardiac biology and disease. However, sarcomeres, the fundamental units of myocyte contraction, are immature and nonlinear in hiPSC-CMs, which technically challenge accurate functional interrogation of contractile parameters in beating cells. Furthermore, existing analysis methods are relatively low-throughput, indirectly assess contractility, or only assess well-aligned sarcomeres found in mature cardiac tissues.
We aimed to develop an analysis platform that directly, rapidly, and automatically tracks sarcomeres in beating cardiomyocytes. The platform should assess sarcomere content, contraction and relaxation parameters, and beat rate.
We developed SarcTrack, a MatLab software that monitors fluorescently tagged sarcomeres in hiPSC-CMs. The algorithm determines sarcomere content, sarcomere length, and returns rates of sarcomere contraction and relaxation. By rapid measurement of hundreds of sarcomeres in each hiPSC-CM, SarcTrack provides large data sets for robust statistical analyses of multiple contractile parameters. We validated SarcTrack by analyzing drug-treated hiPSC-CMs, confirming the contractility effects of compounds that directly activate (CK-1827452) or inhibit (MYK-461) myosin molecules or indirectly alter contractility (verapamil and propranolol). SarcTrack analysis of hiPSC-CMs carrying a heterozygous truncation variant in the myosin-binding protein C ( MYBPC3) gene, which causes hypertrophic cardiomyopathy, recapitulated seminal disease phenotypes including cardiac hypercontractility and diminished relaxation, abnormalities that normalized with MYK-461 treatment.
SarcTrack provides a direct and efficient method to quantitatively assess sarcomere function. By improving existing contractility analysis methods and overcoming technical challenges associated with functional evaluation of hiPSC-CMs, SarcTrack enhances translational prospects for sarcomere-regulating therapeutics and accelerates interrogation of human cardiac genetic variants. |
---|---|
AbstractList | Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR/Cas9 genome editing provide unparalleled opportunities to study cardiac biology and disease. However, sarcomeres, the fundamental units of myocyte contraction, are immature and nonlinear in hiPSC-CMs, which technically challenge accurate functional interrogation of contractile parameters in beating cells. Furthermore, existing analysis methods are relatively low-throughput, indirectly assess contractility, or only assess well-aligned sarcomeres found in mature cardiac tissues.RATIONALEHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR/Cas9 genome editing provide unparalleled opportunities to study cardiac biology and disease. However, sarcomeres, the fundamental units of myocyte contraction, are immature and nonlinear in hiPSC-CMs, which technically challenge accurate functional interrogation of contractile parameters in beating cells. Furthermore, existing analysis methods are relatively low-throughput, indirectly assess contractility, or only assess well-aligned sarcomeres found in mature cardiac tissues.We aimed to develop an analysis platform that directly, rapidly, and automatically tracks sarcomeres in beating cardiomyocytes. The platform should assess sarcomere content, contraction and relaxation parameters, and beat rate.OBJECTIVEWe aimed to develop an analysis platform that directly, rapidly, and automatically tracks sarcomeres in beating cardiomyocytes. The platform should assess sarcomere content, contraction and relaxation parameters, and beat rate.We developed SarcTrack, a MatLab software that monitors fluorescently tagged sarcomeres in hiPSC-CMs. The algorithm determines sarcomere content, sarcomere length, and returns rates of sarcomere contraction and relaxation. By rapid measurement of hundreds of sarcomeres in each hiPSC-CM, SarcTrack provides large data sets for robust statistical analyses of multiple contractile parameters. We validated SarcTrack by analyzing drug-treated hiPSC-CMs, confirming the contractility effects of compounds that directly activate (CK-1827452) or inhibit (MYK-461) myosin molecules or indirectly alter contractility (verapamil and propranolol). SarcTrack analysis of hiPSC-CMs carrying a heterozygous truncation variant in the myosin-binding protein C ( MYBPC3) gene, which causes hypertrophic cardiomyopathy, recapitulated seminal disease phenotypes including cardiac hypercontractility and diminished relaxation, abnormalities that normalized with MYK-461 treatment.METHODS AND RESULTSWe developed SarcTrack, a MatLab software that monitors fluorescently tagged sarcomeres in hiPSC-CMs. The algorithm determines sarcomere content, sarcomere length, and returns rates of sarcomere contraction and relaxation. By rapid measurement of hundreds of sarcomeres in each hiPSC-CM, SarcTrack provides large data sets for robust statistical analyses of multiple contractile parameters. We validated SarcTrack by analyzing drug-treated hiPSC-CMs, confirming the contractility effects of compounds that directly activate (CK-1827452) or inhibit (MYK-461) myosin molecules or indirectly alter contractility (verapamil and propranolol). SarcTrack analysis of hiPSC-CMs carrying a heterozygous truncation variant in the myosin-binding protein C ( MYBPC3) gene, which causes hypertrophic cardiomyopathy, recapitulated seminal disease phenotypes including cardiac hypercontractility and diminished relaxation, abnormalities that normalized with MYK-461 treatment.SarcTrack provides a direct and efficient method to quantitatively assess sarcomere function. By improving existing contractility analysis methods and overcoming technical challenges associated with functional evaluation of hiPSC-CMs, SarcTrack enhances translational prospects for sarcomere-regulating therapeutics and accelerates interrogation of human cardiac genetic variants.CONCLUSIONSSarcTrack provides a direct and efficient method to quantitatively assess sarcomere function. By improving existing contractility analysis methods and overcoming technical challenges associated with functional evaluation of hiPSC-CMs, SarcTrack enhances translational prospects for sarcomere-regulating therapeutics and accelerates interrogation of human cardiac genetic variants. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR/Cas9 genome editing provide unparalleled opportunities to study cardiac biology and disease. However, sarcomeres, the fundamental units of myocyte contraction, are immature and nonlinear in hiPSC-CMs, which technically challenge accurate functional interrogation of contractile parameters in beating cells. Furthermore, existing analysis methods are relatively low-throughput, indirectly assess contractility, or only assess well-aligned sarcomeres found in mature cardiac tissues. We aimed to develop an analysis platform that directly, rapidly, and automatically tracks sarcomeres in beating cardiomyocytes. The platform should assess sarcomere content, contraction and relaxation parameters, and beat rate. We developed SarcTrack, a MatLab software that monitors fluorescently tagged sarcomeres in hiPSC-CMs. The algorithm determines sarcomere content, sarcomere length, and returns rates of sarcomere contraction and relaxation. By rapid measurement of hundreds of sarcomeres in each hiPSC-CM, SarcTrack provides large data sets for robust statistical analyses of multiple contractile parameters. We validated SarcTrack by analyzing drug-treated hiPSC-CMs, confirming the contractility effects of compounds that directly activate (CK-1827452) or inhibit (MYK-461) myosin molecules or indirectly alter contractility (verapamil and propranolol). SarcTrack analysis of hiPSC-CMs carrying a heterozygous truncation variant in the myosin-binding protein C ( MYBPC3) gene, which causes hypertrophic cardiomyopathy, recapitulated seminal disease phenotypes including cardiac hypercontractility and diminished relaxation, abnormalities that normalized with MYK-461 treatment. SarcTrack provides a direct and efficient method to quantitatively assess sarcomere function. By improving existing contractility analysis methods and overcoming technical challenges associated with functional evaluation of hiPSC-CMs, SarcTrack enhances translational prospects for sarcomere-regulating therapeutics and accelerates interrogation of human cardiac genetic variants. |
Author | Neyazi, Meraj Seidman, Christine E Schmid, Manuel Garfinkel, Amanda C Chen, Christopher S Willcox, Jon A L Agarwal, Radhika Cicconet, Marcelo Mücke, Michael Toepfer, Christopher N Rao, Jyoti Chopra, Anant Seidman, Jonathan G Pourquié, Olivier Sharma, Arun Ewoldt, Jourdan |
Author_xml | – sequence: 1 givenname: Christopher N surname: Toepfer fullname: Toepfer, Christopher N organization: Wellcome Centre for Human Genetics (C.N.T.), University of Oxford, United Kingdom – sequence: 2 givenname: Arun surname: Sharma fullname: Sharma, Arun organization: From the Department of Genetics (C.N.T., A.S., A.C.G., M.N., J.A.L.W., R.A., M.S., J.R., O.P., J.G.S., C.E.S.), Harvard Medical School, Boston, MA – sequence: 3 givenname: Marcelo surname: Cicconet fullname: Cicconet, Marcelo organization: Image and Data Analysis Core (M.C.), Harvard Medical School, Boston, MA – sequence: 4 givenname: Amanda C surname: Garfinkel fullname: Garfinkel, Amanda C organization: From the Department of Genetics (C.N.T., A.S., A.C.G., M.N., J.A.L.W., R.A., M.S., J.R., O.P., J.G.S., C.E.S.), Harvard Medical School, Boston, MA – sequence: 5 givenname: Michael surname: Mücke fullname: Mücke, Michael organization: Charité-Universitätsmedizin, Berlin, Germany (M.M.) – sequence: 6 givenname: Meraj surname: Neyazi fullname: Neyazi, Meraj organization: Hannover Medical School, Germany (M.N.) – sequence: 7 givenname: Jon A L surname: Willcox fullname: Willcox, Jon A L organization: From the Department of Genetics (C.N.T., A.S., A.C.G., M.N., J.A.L.W., R.A., M.S., J.R., O.P., J.G.S., C.E.S.), Harvard Medical School, Boston, MA – sequence: 8 givenname: Radhika surname: Agarwal fullname: Agarwal, Radhika organization: From the Department of Genetics (C.N.T., A.S., A.C.G., M.N., J.A.L.W., R.A., M.S., J.R., O.P., J.G.S., C.E.S.), Harvard Medical School, Boston, MA – sequence: 9 givenname: Manuel surname: Schmid fullname: Schmid, Manuel organization: Deutsches Herzzentrum München, Technische Universität München, Germany (M.S.) – sequence: 10 givenname: Jyoti surname: Rao fullname: Rao, Jyoti organization: Harvard Stem Cell Institute, Boston, MA (J.R., O.P.) – sequence: 11 givenname: Jourdan surname: Ewoldt fullname: Ewoldt, Jourdan organization: The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA (J.E., A.C., C.S.C.) – sequence: 12 givenname: Olivier surname: Pourquié fullname: Pourquié, Olivier organization: Harvard Stem Cell Institute, Boston, MA (J.R., O.P.) – sequence: 13 givenname: Anant surname: Chopra fullname: Chopra, Anant organization: The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA (J.E., A.C., C.S.C.) – sequence: 14 givenname: Christopher S surname: Chen fullname: Chen, Christopher S organization: The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA (J.E., A.C., C.S.C.) – sequence: 15 givenname: Jonathan G surname: Seidman fullname: Seidman, Jonathan G organization: From the Department of Genetics (C.N.T., A.S., A.C.G., M.N., J.A.L.W., R.A., M.S., J.R., O.P., J.G.S., C.E.S.), Harvard Medical School, Boston, MA – sequence: 16 givenname: Christine E surname: Seidman fullname: Seidman, Christine E organization: Howard Hughes Medical Institute, Chevy Chase, MD (C.E.S.) |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30700234$$D View this record in MEDLINE/PubMed |
BookMark | eNpNjktLw0AUhQep2LT6E3TtJnXu3LlJZilFq1BwYV2HedxgNI86Yxb-eytWcHXOgY_DtxCzYRxYiEuQK4ACbnwbfeRkX-1hVysETZJORAakdK6phNm_PheLlN6kBI3KnIk5ylJKhToT2bONfhetfz8Xp43tEl8ccyle7u9264d8-7R5XN9uc68MUE6hAHbKWSN9U2gfCmdQU6OpaigwHdyAXEBvrSoQq0pjGUzDKnBwzkpciuvf330cPyZOn3XfJs9dZwcep1QrKI0uFZgf9OqITq7nUO9j29v4Vf_p4zemdEjw |
CitedBy_id | crossref_primary_10_1161_CIRCRESAHA_120_317076 crossref_primary_10_1016_j_jacbts_2023_07_013 crossref_primary_10_1085_jgp_202112928 crossref_primary_10_1016_j_xcrm_2020_100052 crossref_primary_10_1161_RES_0000000000000406 crossref_primary_10_2139_ssrn_3900713 crossref_primary_10_1080_17460441_2020_1722637 crossref_primary_10_1016_j_trsl_2022_08_009 crossref_primary_10_3389_fphys_2021_750364 crossref_primary_10_1016_j_yjmcc_2023_04_008 crossref_primary_10_1371_journal_pone_0252346 crossref_primary_10_1038_s41598_022_26889_2 crossref_primary_10_21105_joss_05322 crossref_primary_10_2139_ssrn_3952830 crossref_primary_10_1007_s12265_022_10348_4 crossref_primary_10_3390_hearts1030018 crossref_primary_10_1111_bph_15228 crossref_primary_10_1161_CIRCGEN_119_002823 crossref_primary_10_1126_sciadv_abo7622 crossref_primary_10_1007_s00424_021_02536_z crossref_primary_10_3389_fcvm_2022_966094 crossref_primary_10_1152_ajpheart_00941_2020 crossref_primary_10_3390_ijms24054724 crossref_primary_10_1016_j_softx_2020_100547 crossref_primary_10_1089_zeb_2023_0015 crossref_primary_10_1002_bit_27582 crossref_primary_10_1371_journal_pone_0300348 crossref_primary_10_1016_j_biopha_2023_116036 crossref_primary_10_1016_j_cophys_2022_100535 crossref_primary_10_1111_febs_16925 crossref_primary_10_1161_CIRCRESAHA_120_316575 crossref_primary_10_3390_cells11081280 crossref_primary_10_1038_s41551_022_00885_3 crossref_primary_10_1016_j_isci_2022_104577 crossref_primary_10_1016_j_yjmcc_2020_03_008 crossref_primary_10_1109_ACCESS_2020_3001191 crossref_primary_10_1016_j_cels_2021_05_001 crossref_primary_10_1016_j_cjca_2023_11_009 crossref_primary_10_3389_fcimb_2023_1098457 crossref_primary_10_1038_s41598_024_52081_9 crossref_primary_10_3389_fcell_2022_986107 crossref_primary_10_1016_j_cmpb_2021_106437 crossref_primary_10_1016_j_yjmcc_2021_09_009 crossref_primary_10_1161_CIRCRESAHA_119_314844 crossref_primary_10_1113_JP279410 crossref_primary_10_1016_j_celrep_2021_109512 crossref_primary_10_1152_ajpheart_00345_2020 crossref_primary_10_1016_j_bbadis_2020_165774 crossref_primary_10_1002_adbi_202000121 crossref_primary_10_1016_j_heliyon_2021_e07671 crossref_primary_10_1016_j_jbc_2022_101867 crossref_primary_10_1242_bio_058568 crossref_primary_10_1016_j_stem_2020_02_011 crossref_primary_10_1161_CIRCRESAHA_120_316966 crossref_primary_10_1371_journal_pcbi_1007676 crossref_primary_10_1021_acsnano_3c06325 crossref_primary_10_3390_biomedicines10030640 crossref_primary_10_1002_cpz1_462 crossref_primary_10_1161_CIRCRESAHA_121_318868 crossref_primary_10_1016_j_snb_2023_134014 crossref_primary_10_1007_s10741_020_10021_5 crossref_primary_10_1063_1_5129347 crossref_primary_10_1063_5_0057434 crossref_primary_10_1172_jci_insight_178131 crossref_primary_10_1161_CIRCRESAHA_119_313569 crossref_primary_10_1002_adhm_201901656 crossref_primary_10_3389_fcvm_2023_1238515 crossref_primary_10_1016_j_bbiosy_2022_100068 crossref_primary_10_1242_bio_060548 crossref_primary_10_1093_cvr_cvac142 crossref_primary_10_1016_j_molmed_2019_06_005 crossref_primary_10_1093_cvr_cvaa124 crossref_primary_10_1016_j_cmpb_2023_107372 crossref_primary_10_1016_j_xcrm_2021_100436 crossref_primary_10_1161_CIRCULATIONAHA_122_059688 crossref_primary_10_1371_journal_pcbi_1009443 crossref_primary_10_1002_ejhf_2414 crossref_primary_10_3389_fcvm_2021_613295 crossref_primary_10_1016_j_phrs_2020_105176 crossref_primary_10_1016_j_stemcr_2023_08_005 crossref_primary_10_1007_s12551_020_00725_1 crossref_primary_10_1161_CIRCULATIONAHA_119_042339 |
ContentType | Journal Article |
DBID | CGR CUY CVF ECM EIF NPM 7X8 |
DOI | 10.1161/circresaha.118.314505 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
DatabaseTitleList | MEDLINE - Academic MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1524-4571 |
ExternalDocumentID | 30700234 |
Genre | Research Support, U.S. Gov't, Non-P.H.S Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
GrantInformation_xml | – fundername: NHLBI NIH HHS grantid: U01 HL098166 – fundername: Wellcome Trust grantid: 206466/Z/17/Z – fundername: NHLBI NIH HHS grantid: R01 HL084553 – fundername: Howard Hughes Medical Institute – fundername: NICHD NIH HHS grantid: R01 HD085121 |
GroupedDBID | --- -~X .-D .3C .Z2 01R 0R~ 18M 1J1 29B 2WC 40H 4Q1 4Q2 4Q3 53G 5GY 5RE 5VS 71W 77Y 7O~ AAAAV AAAXR AAGIX AAHPQ AAIQE AAMOA AAMTA AAQKA AARTV AASCR AASOK AAXQO ABASU ABBUW ABDIG ABJNI ABOCM ABQRW ABVCZ ABXVJ ABZAD ACDDN ACEWG ACGFO ACGFS ACILI ACLDA ACNWC ACPRK ACWDW ACWRI ACXJB ACXNZ ADBBV ADGGA ADHPY AE3 AE6 AENEX AFDTB AFUWQ AGINI AHMBA AHOMT AHQNM AHVBC AIJEX AINUH AJIOK AJNWD AJZMW AKULP ALMA_UNASSIGNED_HOLDINGS ALMTX AMJPA AMKUR AMNEI AOHHW AWKKM BAWUL BOYCO BQLVK C45 CGR CS3 CUY CVF DIK DIWNM DU5 E.X E3Z EBS ECM EEVPB EIF EJD ERAAH EX3 F2K F2L F2M F2N F5P FCALG FL- FRP GNXGY GQDEL GX1 H0~ HLJTE HZ~ IKREB IKYAY IN~ IPNFZ JK3 JK8 K8S KD2 KMI KQ8 L-C L7B N9A NPM N~7 N~B O9- OAG OAH OB2 ODA OK1 OL1 OLG OLH OLU OLV OLW OLY OLZ OPUJH OVD OVDNE OVIDH OVLEI OWW OWY OXXIT P2P PQQKQ RAH RHF RIG RLZ S4R S4S T8P TEORI TR2 TSPGW UPT V2I VVN W3M W8F WH7 WOQ WOW X3V X3W YFH YOC ZFV 7X8 |
ID | FETCH-LOGICAL-c2915-5d61eb2ba90cf64cd6b9345f458f5de516115bd3caa263388437d9fe2dedbba03 |
ISSN | 1524-4571 |
IngestDate | Sat Oct 26 04:08:29 EDT 2024 Sat Nov 02 12:31:11 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 8 |
Keywords | MYK-461 cardiomyocyte contractility myosin binding protein-C cell imaging hypertrophic cardiomyopathy induced pluripotent stem cells sarcomeres |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c2915-5d61eb2ba90cf64cd6b9345f458f5de516115bd3caa263388437d9fe2dedbba03 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
OpenAccessLink | https://doi.org/10.1161/circresaha.118.314505 |
PMID | 30700234 |
PQID | 2179472190 |
PQPubID | 23479 |
ParticipantIDs | proquest_miscellaneous_2179472190 pubmed_primary_30700234 |
PublicationCentury | 2000 |
PublicationDate | 2019-04-12 20190412 |
PublicationDateYYYYMMDD | 2019-04-12 |
PublicationDate_xml | – month: 04 year: 2019 text: 2019-04-12 day: 12 |
PublicationDecade | 2010 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | Circulation research |
PublicationTitleAlternate | Circ Res |
PublicationYear | 2019 |
References | 30973811 - Circ Res. 2019 Apr 12;124(8):1146-1148 |
References_xml | |
SSID | ssj0014329 |
Score | 2.6007745 |
Snippet | Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in combination with CRISPR/Cas9 genome editing provide unparalleled opportunities to... |
SourceID | proquest pubmed |
SourceType | Aggregation Database Index Database |
StartPage | 1172 |
SubjectTerms | Algorithms Benzylamines - antagonists & inhibitors Benzylamines - pharmacology Cardiovascular Agents - pharmacology Carrier Proteins - genetics Clustered Regularly Interspaced Short Palindromic Repeats Computer-Aided Design Fluorescence Humans Induced Pluripotent Stem Cells - drug effects Induced Pluripotent Stem Cells - physiology Microscopy, Atomic Force - methods Myocardial Contraction Myocytes, Cardiac - drug effects Myocytes, Cardiac - physiology Myosins - drug effects Myosins - metabolism Propranolol - pharmacology Sarcomeres - physiology Software Uracil - analogs & derivatives Uracil - antagonists & inhibitors Uracil - pharmacology Urea - analogs & derivatives Urea - pharmacology Verapamil - pharmacology |
Title | SarcTrack |
URI | https://www.ncbi.nlm.nih.gov/pubmed/30700234 https://www.proquest.com/docview/2179472190 |
Volume | 124 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LSwMxEA5aQb2I77coeJOtzSbZJsdS1Co-QLfQ25InFLSV2l789U52s9uCFdRLCIFsNnzDl5lMZgahc62pFYmmkRMSDBRhZCQMNFwkjltBsLQ-wPnhMel06V2P9aZ19PLokrGq68-5cSX_QRXGAFcfJfsHZKuPwgD0AV9oAWFof4XxC0gpHDYhr32Zb6A_0qEm10VI5VNd-aZD--5C6N80q8CMOyZPZJ3zxWhSiU27r8FqtmVsj7avw-rZjhw5sGaDq__NX0uEe9dwk4BzpwiOZ8kvphFlRUmUup0zVjJmEfYcRIPP8B_GRSGe78SceGJu3z63QbBanRaM8DrBlDXY9CQqve-PT9l19_4-S6966SJa8jkOfVmEm171ege0vLwAXfV7ITgLlrmcu8jPBkSuSKTraC1YAKetAs4NtGAHm2j5Ibxx2EIrFarbqHt9lbY7UShYEelYYBYxk2CrYiVFQ7uEapMoQShzlHHHjGXwd5gpQ7SUcUII55Q0jXA2NtYoJRtkB9UGgOceOvXTJI2xo8JSrQSXVpKmhJ7mRmGzj87K_WRACN7LIwd2OPnIYk-xYNeLxj7aLTaavReZSzJP8KCk0YNfzD5Eq1MhOUK18Whij0EBG6uTHIovmkMtHA |
link.rule.ids | 314,780,784,27924,27925 |
linkProvider | Geneva Foundation for Medical Education and Research |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=SarcTrack&rft.jtitle=Circulation+research&rft.au=Toepfer%2C+Christopher+N&rft.au=Sharma%2C+Arun&rft.au=Cicconet%2C+Marcelo&rft.au=Garfinkel%2C+Amanda+C&rft.date=2019-04-12&rft.issn=1524-4571&rft.eissn=1524-4571&rft.volume=124&rft.issue=8&rft.spage=1172&rft_id=info:doi/10.1161%2FCIRCRESAHA.118.314505&rft.externalDBID=NO_FULL_TEXT |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1524-4571&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1524-4571&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1524-4571&client=summon |