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

Waqas Hanif, Linda Alex, Ya Su, Arti V. Shinde, Ilaria Russo, Na Li, Nikolaos G. Frangogiannis

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalCardiovascular Pathology
Volume30
DOIs
StatePublished - Sep 1 2017

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Keywords

  • Atrial remodeling
  • Diabetes
  • Fibrosis
  • Heart failure
  • Hypertrophy
  • Myocardial infarction

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

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