Aortic and Cardiac Structure and Function Using High-Resolution Echocardiography and Optical Coherence Tomography in a Mouse Model of Marfan Syndrome.
Marfan syndrome (MFS) is an autosomal-dominant disorder of connective tissue caused by mutations in the fibrillin-1 (FBN1) gene. Mortality is often due to aortic dissection and rupture. We investigated the structural and functional properties of the heart and aorta in a [Fbn1C1039G/+] MFS mouse using high-resolution ultrasound (echo) and optical coherence tomography (OCT). Echo was performed on 6- and 12-month old wild type (WT) and MFS mice (n = 8). In vivo pulse wave velocity (PWV), aortic root diameter, ejection fraction, stroke volume, left ventricular (LV) wall thickness, LV mass and mitral valve early and atrial velocities (E/A) ratio were measured by high resolution echocardiography. OCT was performed on 12-month old WT and MFS fixed mouse hearts to measure ventricular volume and mass. The PWV was significantly increased in 6-mo MFS vs. WT (366.6 ± 19.9 vs. 205.2 ± 18.1 cm/s; p = 0.003) and 12-mo MFS vs. WT (459.5 ± 42.3 vs. 205.3 ± 30.3 cm/s; p< 0.0001). PWV increased with age in MFS mice only. We also found a significantly enlarged aortic root and decreased E/A ratio in MFS mice compared with WT for both age groups. The [Fbn1C1039G/+] mouse model of MFS replicates many of the anomalies of Marfan patients including significant aortic dilation, central aortic stiffness, LV systolic and diastolic dysfunction. This is the first demonstration of the direct measurement in vivo of pulse wave velocity non-invasively in the aortic arch of MFS mice, a robust measure of aortic stiffness and a critical clinical parameter for the assessment of pathology in the Marfan syndrome.
Child and Family Research Institute, Department of Cardiovascular Sciences, Vancouver, BC, Canada.|Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
Ling
L
Lee
Child and Family Research Institute, Department of Cardiovascular Sciences, Vancouver, BC, Canada.|Division of Cardiology, Department of Pediatrics, UBC, Vancouver, BC, Canada.
Jason Z
JZ
Cui
School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.
Michelle
M
Cua
Child and Family Research Institute, Department of Cardiovascular Sciences, Vancouver, BC, Canada.|Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Mitra
M
Esfandiarei
Child and Family Research Institute, Department of Cardiovascular Sciences, Vancouver, BC, Canada.|Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
Xiaoye
X
Sheng
School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.
Winsey Audrey
WA
Chui
Child and Family Research Institute, Department of Cardiovascular Sciences, Vancouver, BC, Canada.
Michael Haoying
MH
Xu
School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.
Marinko V
MV
Sarunic
School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.
Mirza Faisal
MF
Beg
Child and Family Research Institute, Department of Cardiovascular Sciences, Vancouver, BC, Canada.|Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Cornelius
C
van Breemen
Child and Family Research Institute, Department of Cardiovascular Sciences, Vancouver, BC, Canada.|Division of Cardiology, Department of Pediatrics, UBC, Vancouver, BC, Canada.
George G S
GG
Sandor
Child and Family Research Institute, Department of Cardiovascular Sciences, Vancouver, BC, Canada.|Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
Glen F
http://orcid.org/0000-0002-2586-3115
GF
Tibbits
D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology*; D001021:Aortic Valve / Q000503:physiopathology; D004195:Disease Models, Animal; D004452:Echocardiography / Q000379:methods; D006325:Heart Atria / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology*; D008382:Marfan Syndrome / Q000503:physiopathology*; D051379:Mice; D063177:Pulse Wave Analysis / Q000379:methods; D013318:Stroke Volume / Q000502:physiology; D041623:Tomography, Optical Coherence / Q000379:methods; D059289:Vascular Stiffness / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology