title: Overexpression of myeloid differentiation protein 88 in mice induces mild cardiac dysfunction, but no deficit in heart morphology.
abstract: Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=∼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.
authors.affiliation: Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University, Suzhou, Jiangsu, China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Surgery, East Tennessee State University, Johnson City, TN, USA.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: X
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015153:Blotting, Western; D004452:Echocardiography; D006331:Heart Diseases / Q000378:metabolism / Q000503:physiopathology*; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D063305:Organ Dysfunction Scores; D009929:Organ Size; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor