دورية أكاديمية
أعرض في EDS

In vivo visualization and molecular targeting of the cardiac conduction system.

التفاصيل البيبلوغرافية
العنوان: In vivo visualization and molecular targeting of the cardiac conduction system.
المؤلفون: Goodyer WR; Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA.; Department of Pediatrics, Stanford University, Stanford, California, USA., Beyersdorf BM; Department of Cardiovascular Surgery, Institute Insure (Institute for Translational Cardiac Surgery), German Heart Center Munich, Technische Universität München, Munich, Germany., Duan L; Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA., van den Berg NS; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California, USA., Mantri S; Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA., Galdos FX; Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA., Puluca N; Department of Cardiovascular Surgery, Institute Insure (Institute for Translational Cardiac Surgery), German Heart Center Munich, Technische Universität München, Munich, Germany., Buikema JW; Department of Cardiology, Utrecht Regenerative Medicine Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.; Department of Cardiology, Amsterdam University Medical Center, Location VUmc, Amsterdam, Netherlands., Lee S; Department of Pharmacy, Bioconvergence Program, Sungkyunkwan University, Suwon, South Korea., Salmi D; Department of Pathology and., Robinson ER; Department of Radiology, Stanford University, Stanford, California, USA., Rogalla S; Division of Gastroenterology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA., Cogan DP; Departments of Chemistry and Chemical Engineering and Sarafan ChEM-H Institute, Stanford University, Stanford, California, USA., Khosla C; Departments of Chemistry and Chemical Engineering and Sarafan ChEM-H Institute, Stanford University, Stanford, California, USA., Rosenthal EL; Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Wu SM; Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA.; Department of Pediatrics, Stanford University, Stanford, California, USA.; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
المصدر: The Journal of clinical investigation [J Clin Invest] 2022 Oct 17; Vol. 132 (20). Date of Electronic Publication: 2022 Oct 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: Heart Conduction System*/metabolism , Molecular Targeted Therapy*, Animals ; Arrhythmias, Cardiac/genetics ; Arrhythmias, Cardiac/metabolism ; Heart/physiology ; Humans ; Mice ; Myocardium
مستخلص: Accidental injury to the cardiac conduction system (CCS), a network of specialized cells embedded within the heart and indistinguishable from the surrounding heart muscle tissue, is a major complication in cardiac surgeries. Here, we addressed this unmet need by engineering targeted antibody-dye conjugates directed against the CCS, allowing for the visualization of the CCS in vivo following a single intravenous injection in mice. These optical imaging tools showed high sensitivity, specificity, and resolution, with no adverse effects on CCS function. Further, with the goal of creating a viable prototype for human use, we generated a fully human monoclonal Fab that similarly targets the CCS with high specificity. We demonstrate that, when conjugated to an alternative cargo, this Fab can also be used to modulate CCS biology in vivo, providing a proof of principle for targeted cardiac therapeutics. Finally, in performing differential gene expression analyses of the entire murine CCS at single-cell resolution, we uncovered and validated a suite of additional cell surface markers that can be used to molecularly target the distinct subcomponents of the CCS, each prone to distinct life-threatening arrhythmias. These findings lay the foundation for translational approaches targeting the CCS for visualization and therapy in cardiothoracic surgery, cardiac imaging, and arrhythmia management.
التعليقات: Comment in: J Clin Invest. 2022 Oct 17;132(20):. (PMID: 36250459)
References: Cardiol Res Pract. 2014;2014:615987. (PMID: 24511410)
J Clin Invest. 2016 Dec 1;126(12):4444-4459. (PMID: 27775552)
Nat Rev Cardiol. 2018 Oct;15(10):617-630. (PMID: 29875439)
Trends Mol Med. 2015 Dec;21(12):749-761. (PMID: 26611337)
Nat Biotechnol. 2018 Jun;36(5):411-420. (PMID: 29608179)
J Am Heart Assoc. 2017 Dec 21;6(12):. (PMID: 29269355)
Circ Arrhythm Electrophysiol. 2010 Apr;3(2):186-94. (PMID: 20110552)
Am J Cardiol. 2015 Feb 1;115(3):316-22. (PMID: 25491240)
Mol Imaging Biol. 2010 Dec;12(6):583-94. (PMID: 20376568)
Front Pediatr. 2019 Feb 11;7:23. (PMID: 30805324)
Dev Cell. 2012 Jul 17;23(1):21-34. (PMID: 22814600)
Pediatr Med Chir. 1998 May-Jun;20(3):181-6. (PMID: 9744009)
Curr Opin Pharmacol. 2012 Oct;12(5):615-22. (PMID: 22920732)
Cancer Res. 2018 Sep 1;78(17):5144-5154. (PMID: 29967260)
Cell. 2016 Jun 16;165(7):1789-1802. (PMID: 27238021)
Rev Esp Cardiol. 2003 Nov;56(11):1085-92. (PMID: 14622540)
Surg Oncol. 2018 Jun;27(2):225-230. (PMID: 29937175)
Ann Surg Oncol. 2009 Oct;16(10):2943-52. (PMID: 19582506)
Cell. 2015 May 21;161(5):1202-1214. (PMID: 26000488)
Eur J Heart Fail. 2018 Oct;20(10):1472-1481. (PMID: 29251799)
Pacing Clin Electrophysiol. 2010 Jun 1;33(6):754-62. (PMID: 20180918)
Lancet Oncol. 2019 Jul;20(7):e354-e367. (PMID: 31267970)
Semin Thorac Cardiovasc Surg. 2019 Autumn;31(3):537-546. (PMID: 30738149)
Heart Rhythm. 2020 Dec;17(12):2200-2207. (PMID: 32659372)
Circ Res. 2006 Jun 9;98(11):1422-30. (PMID: 16690884)
Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4327-32. (PMID: 10759566)
Biochem Biophys Res Commun. 2001 Feb 16;281(1):220-6. (PMID: 11178983)
Bioinformatics. 2020 Jun 1;36(11):3447-3456. (PMID: 32053146)
Circ Res. 2019 Aug 2;125(4):379-397. (PMID: 31284824)
Mol Imaging Biol. 2015 Feb;17(1):49-57. (PMID: 25080323)
Nat Rev Clin Oncol. 2013 Sep;10(9):507-18. (PMID: 23881033)
Heart Rhythm. 2006 May;3(5):601-4. (PMID: 16648069)
Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515. (PMID: 30395287)
Clin Cancer Res. 2015 Aug 15;21(16):3658-66. (PMID: 25904751)
J Thorac Cardiovasc Surg. 2019 Mar;157(3):1168-1177.e2. (PMID: 30917883)
Auton Neurosci. 2017 Nov;207:48-58. (PMID: 28802636)
معلومات مُعتمدة: R01 CA238686 United States CA NCI NIH HHS; P30 NS069375 United States NS NINDS NIH HHS; DP1 LM012179 United States LM NLM NIH HHS; K08 HL153785 United States HL NHLBI NIH HHS; S10 OD025091 United States OD NIH HHS; R01 CA239257 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Arrhythmias; Cardiology; Cardiovascular disease; Diagnostic imaging
تواريخ الأحداث: Date Created: 20220811 Date Completed: 20221018 Latest Revision: 20240214
رمز التحديث: 20240214
مُعرف محوري في PubMed: PMC9566899
DOI: 10.1172/JCI156955
PMID: 35951416
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI156955