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Quantification of cardiomyocyte hypertrophy by cardiac magnetic resonance: implications for early cardiac remodeling.

Abstract：

BACKGROUND:Cardiomyocyte hypertrophy is a critical precursor to the development of heart failure. Methods to phenotype cellular hypertrophy noninvasively are limited. The goal was to validate a cardiac magnetic resonance-based approach for the combined assessment of extracellular matrix expansion and cardiomyocyte hypertrophy. METHODS AND RESULTS:Two murine models of hypertension (n=18, with n=15 controls) induced by l-N(G)-nitroarginine methyl ester (L-NAME) and pressure overload (n=11) from transaortic constriction (TAC) were imaged by cardiac magnetic resonance at baseline and 7 weeks after L-NAME treatment or up to 7 weeks after TAC. T1 relaxation times were measured before and after gadolinium contrast. The intracellular lifetime of water (τic), a cell size-dependent parameter, and extracellular volume fraction, a marker of interstitial fibrosis, were determined with a model for transcytolemmal water exchange. Cardiomyocyte diameter and length were measured on FITC-wheat germ agglutinin-stained sections. The τic correlated strongly with histological cardiomyocyte volume-to-surface ratio (r=0.78, P<0.001) and cell volume (r=0.75, P<0.001). Histological cardiomyocyte diameters and cell volumes were higher in mice treated with L-NAME compared with controls (P<0.001). In the TAC model, cardiac magnetic resonance and histology showed cell hypertrophy at 2 weeks after TAC without significant fibrosis at this early time point. Mice exposed to TAC demonstrated a significant, longitudinal, and parallel increase in histological cell volume, volume-to-surface ratio, and τic between 2 and 7 weeks after TAC. CONCLUSION:The τic measured by contrast-enhanced cardiac magnetic resonance provides a noninvasive measure of cardiomyocyte hypertrophy. Extracellular volume fraction and τic can track myocardial tissue remodeling from pressure overload.

journal_name

Circulation

journal_title

Circulation

authors

Coelho-Filho OR,Shah RV,Mitchell R,Neilan TG,Moreno H Jr,Simonson B,Kwong R,Rosenzweig A,Das S,Jerosch-Herold M

doi

10.1161/CIRCULATIONAHA.112.000438

subject

Has Abstract

pub_date

2013-09-10 00:00:00

pages

1225-33

issue

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.112.000438

journal_volume

128

pub_type

杂志文章

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Quantification of cardiomyocyte hypertrophy by cardiac magnetic resonance: implications for early cardiac remodeling.