Left atrial remodeling, hypertrophy, and fibrosis in mouse models of heart failure

• Published in: Cardiovascular pathology Vol. 30; pp. 27 - 37
• Main Authors: Hanif, Waqas, Alex, Linda, Su, Ya, Shinde, Arti V, Russo, Ilaria, Li, Na, Frangogiannis, Nikolaos G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2017
• Subjects: Animals; Atrial remodeling; Atrial Remodeling - physiology; Cardiomegaly - etiology; Cardiomegaly - pathology; Cardiomegaly - physiopathology; Connexin 43 - metabolism; Diabetes; Diabetic Cardiomyopathies - pathology; Diabetic Cardiomyopathies - physiopathology; Disease Models, Animal; Female; Fibrosis; Heart failure; Heart Failure - etiology; Heart Failure - pathology; Heart Failure - physiopathology; Humans; Hypertrophy; Male; Mice; Mice, Inbred C57BL; Myocardial infarction; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Obesity - pathology; Obesity - physiopathology; Pathology; Tachycardia - pathology; Tachycardia - physiopathology; Ventricular Dysfunction, Left - pathology; Ventricular Dysfunction, Left - physiopathology; Myocardial infarction; Heart failure; Diabetes; Atrial remodeling; Fibrosis; Hypertrophy; heart failure; atrial remodeling; fibrosis; hypertrophy; diabetes; myocardial infarction
• ISSN: 1054-8807; 1879-1336; 1879-1336
• DOI: 10.1016/j.carpath.2017.06.003

Left ventricular dysfunction increases left atrial pressures and causes atrial remodeling. In human subjects, increased left atrial size is a powerful predictor of mortality and adverse events in a broad range of cardiac pathologic conditions. Moreover, structural remodeling of the atrium plays an important role in the pathogenesis of atrial tachyarrhythmias. Despite the potential value of the atrium in assessment of functional endpoints in myocardial disease, atrial pathologic alterations in mouse models of left ventricular disease have not been systematically investigated. Our study describes the geometric, morphologic, and structural changes in experimental mouse models of cardiac pressure overload (induced through transverse aortic constriction), myocardial infarction, and diabetes. Morphometric and histological analysis showed that pressure overload was associated with left atrial dilation, increased left atrial mass, loss of myofibrillar content in a subset of atrial cardiomyocytes, atrial cardiomyocyte hypertrophy, and atrial fibrosis. In mice undergoing nonreperfused myocardial infarction protocols, marked left ventricular systolic dysfunction was associated with left atrial enlargement, atrial cardiomyocyte hypertrophy, and atrial fibrosis. Both infarcted animals and pressure overloaded mice exhibited attenuation and perturbed localization of atrial connexin-43 immunoreactivity, suggesting gap junctional remodeling. In the absence of injury, obese diabetic db/db mice had diastolic dysfunction associated with atrial dilation, atrial cardiomyocyte hypertrophy, and mild atrial fibrosis. Considering the challenges in assessment of clinically relevant functional endpoints in mouse models of heart disease, study of atrial geometry and morphology may serve as an important new tool for evaluation of ventricular function. •In a mouse model of cardiac pressure overload, left ventricular remodeling is associated with left atrial dilation, hypertrophy, and fibrosis.•Following left ventricular infarction, mice exhibit marked left atrial remodeling and fibrosis.•Obese diabetic mice have atrial dilation, hypertrophy, and mild atrial fibrosis.•Mice with postinfarction heart failure or pressure overload exhibit myofibrillar loss in atrial cardiomyocytes and perturbed localization of connexin-43.