Journal article
Acute Catecholamine Exposure Causes Reversible Myocyte Injury Without Cardiac Regeneration
Circulation research, v 119(7), pp 865-879
16 Sep 2016
PMID: 27461939
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Catecholamines increase cardiac contractility, but exposure to high concentrations or prolonged exposures can cause cardiac injury. A recent study demonstrated that a single subcutaneous injection of isoproterenol (ISO; 200 mg/kg) in mice causes acute myocyte death (8%-10%) with complete cardiac repair within a month. Cardiac regeneration was via endogenous cKit(+) cardiac stem cell-mediated new myocyte formation.
Our goal was to validate this simple injury/regeneration system and use it to study the biology of newly forming adult cardiac myocytes.
C57BL/6 mice (n=173) were treated with single injections of vehicle, 200 or 300 mg/kg ISO, or 2 daily doses of 200 mg/kg ISO for 6 days. Echocardiography revealed transiently increased systolic function and unaltered diastolic function 1 day after single ISO injection. Single ISO injections also caused membrane injury in ≈10% of myocytes, but few of these myocytes appeared to be necrotic. Circulating troponin I levels after ISO were elevated, further documenting myocyte damage. However, myocyte apoptosis was not increased after ISO injury. Heart weight to body weight ratio and fibrosis were also not altered 28 days after ISO injection. Single- or multiple-dose ISO injury was not associated with an increase in the percentage of 5-ethynyl-2'-deoxyuridine-labeled myocytes. Furthermore, ISO injections did not increase new myocytes in cKit(+/Cre)×R-GFP transgenic mice.
A single dose of ISO causes injury in ≈10% of the cardiomyocytes. However, most of these myocytes seem to recover and do not elicit cKit(+) cardiac stem cell-derived myocyte regeneration.
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Details
- Title
- Acute Catecholamine Exposure Causes Reversible Myocyte Injury Without Cardiac Regeneration
- Creators
- Markus Wallner - Temple UniversityJason M Duran - Temple UniversitySadia Mohsin - Temple UniversityConstantine D Troupes - Temple UniversityDavy Vanhoutte - Cincinnati Children's Hospital Medical CenterGiulia Borghetti - Temple UniversityRonald J Vagnozzi - Cincinnati Children's Hospital Medical CenterPolina Gross - Temple UniversityDaohai Yu - Temple UniversityDanielle M Trappanese - Temple UniversityHajime Kubo - Temple UniversityAmir Toib - Drexel UniversityThomas E Sharp, 3rdShavonn C Harper - Temple UniversityMichael A Volkert - Temple UniversityTimothy Starosta - Temple UniversityEric A Feldsott - Temple UniversityRemus M Berretta - Temple UniversityTao Wang - Temple UniversityMary F Barbe - Temple UniversityJeffrey D Molkentin - Cincinnati Children's Hospital Medical CenterSteven R Houser - Temple University
- Publication Details
- Circulation research, v 119(7), pp 865-879
- Grant note
- 15SDG25550038 / American Heart Association-American Stroke Association T32 HL091804 / NHLBI NIH HHS R01 HL119229 / NHLBI NIH HHS R01 HL033921 / NHLBI NIH HHS P01 HL091799 / NHLBI NIH HHS R01 HL089312 / NHLBI NIH HHS P01 HL108806 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000384001200015
- Scopus ID
- 2-s2.0-84988423522
- Other Identifier
- 991019168580204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Hematology
- Peripheral Vascular Disease