دورية أكاديمية
أعرض في EDS

Accelerated Marfan syndrome model recapitulates established signaling pathways.

التفاصيل البيبلوغرافية
العنوان: Accelerated Marfan syndrome model recapitulates established signaling pathways.
المؤلفون: Gensicke NM; University of Iowa Carver College of Medicine, Iowa City, Iowa., Cavanaugh NB; Marian University College of Osteopathic Medicine, Indianapolis, Ind., Andersen ND; Duke Congenital Heart Surgery Research & Training Laboratory, Durham, NC; Duke Pediatric & Congenital Heart Center of Duke Children's Hospital, Durham, NC; Division of Thoracic and Cardiovascular Surgery, Duke University Medical Center, Durham, NC., Huang T; Duke Congenital Heart Surgery Research & Training Laboratory, Durham, NC., Qian L; University of Iowa Carver College of Medicine, Iowa City, Iowa., Dyle MC; University of Iowa Carver College of Medicine, Iowa City, Iowa., Turek JW; Duke Congenital Heart Surgery Research & Training Laboratory, Durham, NC; Duke Pediatric & Congenital Heart Center of Duke Children's Hospital, Durham, NC; Division of Thoracic and Cardiovascular Surgery, Duke University Medical Center, Durham, NC. Electronic address: joseph.turek@duke.edu.
المصدر: The Journal of thoracic and cardiovascular surgery [J Thorac Cardiovasc Surg] 2020 May; Vol. 159 (5), pp. 1719-1726. Date of Electronic Publication: 2019 May 31.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Mosby Country of Publication: United States NLM ID: 0376343 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-685X (Electronic) Linking ISSN: 00225223 NLM ISO Abbreviation: J Thorac Cardiovasc Surg Subsets: MEDLINE
أسماء مطبوعة: Publication: St. Louis, MO : Mosby
Original Publication: St. Louis.
مواضيع طبية MeSH: Aorta/*metabolism , Aortic Aneurysm/*metabolism , Cardiomyopathies/*metabolism , Marfan Syndrome/*metabolism , Myocardium/*metabolism, Angiotensin II ; Animals ; Aorta/pathology ; Aortic Aneurysm/chemically induced ; Aortic Aneurysm/genetics ; Aortic Aneurysm/pathology ; Cardiomyopathies/genetics ; Cardiomyopathies/pathology ; Dilatation, Pathologic ; Disease Models, Animal ; Disease Progression ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibrillin-1/genetics ; Genetic Predisposition to Disease ; Heterozygote ; Marfan Syndrome/complications ; Marfan Syndrome/genetics ; Mice, Mutant Strains ; Mutation ; Myocardium/pathology ; Phenotype ; Phosphorylation ; Signal Transduction ; Smad2 Protein/metabolism ; Time Factors ; Transforming Growth Factor beta/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism
مستخلص: Objective: Marfan syndrome (MFS) represents a genetic disorder with a range of clinical features, including proximal aortic aneurysms. Extensive research has revealed an abundance of transforming growth factor beta from a mutation in fibrillin-1 to be the key biochemical mechanism of aneurysm formation. Many important signaling pathways downstream of transforming growth factor beta have been further characterized. Our laboratory has previously demonstrated a unique murine model of MFS resulting in the accelerated formation of ascending aortic aneurysms and dilated cardiomyopathies. This study aims to characterize the relevance of this model to known signaling mechanisms in MFS.
Methods: Fibrillin 1C 1039G/+ heterozygous mice (ie, MFS), with a mutation in fibrillin-1, were supplemented with 4.5 mg/kg/d angiotensin II to accelerate aneurysm formation. Four mouse groups were analyzed: wild type with or without angiotensin II and MFS with or without angiotensin II. Aortic tissue from these samples were subjected to western blotting and phosphoimaging to query various signaling pathways.
Results: Mice with MFS displayed downstream regulation in both the canonical (Smad2) and noncononical (extracellular signal-regulated kinases and P38) pathways characteristic of MFS. However, these downstream signals were exaggerated in the MFS mice supplemented with angiotensin II (accelerated model), matching the observed phenotypic severity of this model.
Conclusions: The murine MFS model depicted here accelerates ascending aortic aneurysm formation and cardiomyopathies via well-characterized MFS signaling cascades. The mechanistic relevance of the accelerated murine MFS model suggests that it could be an important tool in future studies hoping to characterize MFS signaling in an expedited experimental design.
(Copyright © 2019 The American Association for Thoracic Surgery. All rights reserved.)
التعليقات: Comment in: J Thorac Cardiovasc Surg. 2020 May;159(5):1727-1728. (PMID: 31230809)
Comment in: J Thorac Cardiovasc Surg. 2020 May;159(5):1729. (PMID: 31358331)
فهرسة مساهمة: Keywords: Erk; Marfan syndrome; Smad2; aortopathy; cardiomyopathy; fibrillin-1; p38
المشرفين على المادة: 0 (Fbn1 protein, mouse)
0 (Fibrillin-1)
0 (Smad2 Protein)
0 (Smad2 protein, mouse)
0 (Transforming Growth Factor beta)
11128-99-7 (Angiotensin II)
EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
تواريخ الأحداث: Date Created: 20190706 Date Completed: 20200622 Latest Revision: 20200622
رمز التحديث: 20240628
DOI: 10.1016/j.jtcvs.2019.05.043
PMID: 31272746
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-685X
DOI:10.1016/j.jtcvs.2019.05.043