Mouse heart valve structure and function: echocardiographic and morphometric analyses from the fetus through the aged adult.

The purpose of this study is to provide standard echocardiographic and morphometric data for normal mouse valve structure and function from late fetal to aged adult stages. Cross-sectional, two-dimensional and Doppler transthoracic echocardiography was performed in C57BL6 mice anesthetized with 1% to 2% isoflurane at embryonic day 18.5 (late fetal), 10 days (neonate), 1 mo (juvenile), 2 mo (young adult), 9 mo (old adult), and 16 mo (aged adult). Normal annulus dimensions indexed to age or weight, and selected flow velocities, were established by echocardiography. After echocardiographic imaging, hearts were harvested and histological and morphometric analyses were performed. Morphometric analysis demonstrated a progressive valve thinning and elongation during the fetal and juvenile stages that plateaued during adult stages (ANOVA, P < 0.01); however, there was increased thickening of the hinge of the aortic valve with advanced age, reminiscent of human aortic valve sclerosis. There was no age-related calcification. The results of this study provide comprehensive echocardiographic and morphometric data for normal mouse valve structure and function from late fetal to aged adult stages and should prove useful as a reference standard for future studies using mouse models of progressive valve disease.

[1]  Richard P. Harvey,et al.  Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7 , 2007, Proceedings of the National Academy of Sciences.

[2]  R. Kist,et al.  Sox9 is required for precursor cell expansion and extracellular matrix organization during mouse heart valve development. , 2007, Developmental biology.

[3]  Jeffrey Robbins,et al.  Principles of genetic murine models for cardiac disease. , 2007, Circulation.

[4]  V. Gaussin,et al.  Atrioventricular valve development during late embryonic and postnatal stages involves condensation and extracellular matrix remodeling. , 2007, Developmental biology.

[5]  E. Foster,et al.  Validation of the wall motion score and myocardial performance indexes as novel techniques to assess cardiac function in mice after myocardial infarction. , 2007, American journal of physiology. Heart and circulatory physiology.

[6]  J. Rottman,et al.  Echocardiographic Evaluation of Ventricular Function in Mice , 2007, Echocardiography.

[7]  S. Young,et al.  Calcific Aortic Valve Stenosis in Old Hypercholesterolemic Mice , 2006, Circulation.

[8]  Shinsuke Yuasa,et al.  Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis , 2006, Nature Medicine.

[9]  Colin K. L. Phoon,et al.  Imaging Tools for the Developmental Biologist: Ultrasound Biomicroscopy of Mouse Embryonic Development , 2006, Pediatric Research.

[10]  R. Hinton,et al.  Extracellular Matrix Remodeling and Organization in Developing and Diseased Aortic Valves , 2006, Circulation research.

[11]  F. Schoen,et al.  Human Semilunar Cardiac Valve Remodeling by Activated Cells From Fetus to Adult: Implications for Postnatal Adaptation, Pathology, and Tissue Engineering , 2006, Circulation.

[12]  William Stewart,et al.  Recommendations for chamber quantification. , 2006, European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology.

[13]  Y. Deshaies,et al.  A high fat/high carbohydrate diet induces aortic valve disease in C57BL/6J mice. , 2006, Journal of the American College of Cardiology.

[14]  G. Breithardt,et al.  Age and gender related reference values for transthoracic Doppler-echocardiography in the anesthetized CD1 mouse , 2006, The International Journal of Cardiovascular Imaging.

[15]  R. Norris,et al.  Normal distribution of melanocytes in the mouse heart. , 2005, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[16]  Y. Suematsu,et al.  Age-associated aortic stenosis in apolipoprotein E-deficient mice. , 2005, Journal of the American College of Cardiology.

[17]  R. Hinton,et al.  Congenital heart disease: Genetic causes and developmental insights , 2005 .

[18]  W. Roberts,et al.  Frequency by Decades of Unicuspid, Bicuspid, and Tricuspid Aortic Valves in Adults Having Isolated Aortic Valve Replacement for Aortic Stenosis, With or Without Associated Aortic Regurgitation , 2005, Circulation.

[19]  D. Judge,et al.  TGF-β–dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome , 2004 .

[20]  L. Leatherbury,et al.  High-frequency ultrasound database profiling growth, development, and cardiovascular function in C57BL/6J mouse fetuses. , 2004, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[21]  Orlando Aristizábal,et al.  Embryonic Heart Failure in NFATc1−/− Mice: Novel Mechanistic Insights From In Utero Ultrasound Biomicroscopy , 2004, Circulation research.

[22]  Katherine E Yutzey,et al.  Development of heart valve leaflets and supporting apparatus in chicken and mouse embryos , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[23]  D. Judge,et al.  TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. , 2004, The Journal of clinical investigation.

[24]  C. Peters,et al.  Cardiac and Ocular Pathologies in a Mouse Model of Mucopolysaccharidosis Type VI , 2003, Pediatric Research.

[25]  Pamela S Douglas,et al.  Acc/aha/ase 2003 Guideline Update for the Clinical Application of Echocardiography: Summary Article a Report of the American College of Cardiology/american Heart Association Task Force on Practice Guidelines (acc/aha/ase Committee to Update the 1997 Guidelines for the Clinical Application of Echocar , 2003 .

[26]  Claudia E Korcarz,et al.  Use of echocardiography for the phenotypic assessment of genetically altered mice. , 2003, Physiological genomics.

[27]  Natesa G Pandian,et al.  Use of pulse wave and color flow Doppler echocardiography in mouse models of human disease. , 2002, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[28]  E. Gilpin,et al.  Impact of anesthesia on cardiac function during echocardiography in mice. , 2002, American journal of physiology. Heart and circulatory physiology.

[29]  R. Levy,et al.  Matrix metalloproteinase-2 is associated with tenascin-C in calcific aortic stenosis. , 2001, The American journal of pathology.

[30]  T. Doetschman,et al.  Double-Outlet Right Ventricle and Overriding Tricuspid Valve Reflect Disturbances of Looping, Myocardialization, Endocardial Cushion Differentiation, and Apoptosis in TGF-β2–Knockout Mice , 2001 .

[31]  S. Shroff,et al.  Accuracy of echocardiographic estimates of left ventricular mass in mice. , 2001, American journal of physiology. Heart and circulatory physiology.

[32]  T. Doetschman,et al.  Double-outlet right ventricle and overriding tricuspid valve reflect disturbances of looping, myocardialization, endocardial cushion differentiation, and apoptosis in TGF-beta(2)-knockout mice. , 2001, Circulation.

[33]  G. Jennings,et al.  Age-dependent cardiomyopathy and heart failure phenotype in mice overexpressing beta(2)-adrenergic receptors in the heart. , 2000, Cardiovascular research.

[34]  R. Anderson.  Clinical anatomy of the aortic root , 2000, Heart.

[35]  P J Kilner,et al.  The aortic outflow and root: a tale of dynamism and crosstalk. , 1999, The Annals of thoracic surgery.

[36]  Bonnie K. Lind,et al.  Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. , 1999, The New England journal of medicine.

[37]  R. Weintraub,et al.  Relationship of the dimension of cardiac structures to body size: an echocardiographic study in normal infants and children , 1999, Cardiology in the Young.

[38]  F. Kern.  Echocardiography in Pediatric Heart Disease. 2nd ed , 1998 .

[39]  K. Chien,et al.  Physiological assessment of complex cardiac phenotypes in genetically engineered mice. , 1997, The American journal of physiology.

[40]  L. Hatle,et al.  Doppler evaluation of left and right ventricular diastolic function: a technical guide for obtaining optimal flow velocity recordings. , 1997, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[41]  N. Silverman,et al.  Echocardiographic evaluation of congenital mitral valve anomalies in children. , 1995, The American journal of cardiology.

[42]  J. Gardin,et al.  Echocardiographic assessment of left ventricular mass and systolic function in mice. , 1995, Circulation research.

[43]  T. Tacy,et al.  Range of normal valve annulus size in neonates. , 1995, The American journal of cardiology.

[44]  A. Gown,et al.  Characterization of the Early Lesion of ‘Degenerative’ Valvular Aortic Stenosis: Histological and Immunohistochemical Studies , 1994, Circulation.

[45]  M McLean,et al.  Three-dimensional reconstruction from serial sections. V. Calibration of dimensional changes incurred during tissue preparation and data processing. , 1991, Analytical and quantitative cytology and histology.

[46]  Doppler Assessment of Right Ventricular Filling in a Normal Population: Comparison with Left Ventricular Filling Dynamics , 1991 .

[47]  M. Quiñones,et al.  Doppler assessment of right ventricular filling in a normal population. Comparison with left ventricular filling dynamics. , 1990, Circulation.

[48]  A. R. Snider,et al.  Echocardiography in Pediatric Heart Disease , 1990 .

[49]  C. Rembold,et al.  Growth of the human heart relative to body surface area. , 1990, The American journal of cardiology.

[50]  L. Hatle,et al.  Noninvasive estimation of valve area in patients with aortic stenosis by Doppler ultrasound and two-dimensional echocardiography. , 1985, Circulation.

[51]  J. D. Cornelius.  Inheritance of mitral valve prolapse: Effect of age and sex on gene expression , 1984 .

[52]  A. R. Snider,et al.  Two-dimensional echocardiographic determination of aortic and pulmonary artery sizes from infancy to adulthood in normal subjects. , 1984, The American journal of cardiology.

[53]  A. Gerdes,et al.  Morphometric study of cardiac muscle: the problem of tissue shrinkage. , 1982, Laboratory investigation; a journal of technical methods and pathology.

[54]  R. Lefkowitz,et al.  Adrenergic receptors in the heart. , 1982, Annual review of physiology.

[55]  D. C. Sheehan,et al.  Theory and Practice of Histotechnology , 1980 .

[56]  CYRUS LEVINTHAL,et al.  Three Dimensional Reconstruction from Serial Sections , 1972, Nature.

[57]  A M Rudolph,et al.  The Circulation of the Fetus in Utero: Methods For Studying Distribution of Blood Flow, Cardiac Output And Organ Blood Flow , 1967, Circulation research.