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Cardiac fibrosis and diastolic dysfunction are highly correlated in a mouse chronic pressure‐overload model
Author(s) -
Olzinski Alan,
Bao Weike,
DeLong Drew,
Lenhard Steve,
Wright Fe,
Coatney Robert,
Jucker Beat,
Eisennagel Stephen,
Needle Saul,
Wang Tao,
Schnackenberg Christine
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1129.6
Subject(s) - diastole , fibrosis , ventricle , medicine , pressure overload , cardiac fibrosis , cardiology , myocardial fibrosis , hydroxyproline , pulse pressure , heart failure , blood pressure , cardiac hypertrophy
The purpose of this study was to determine which measurements of diastolic dysfunction are most correlated with cardiac fibrosis. Mice were subjected to Sham (n=7) or transverse aortic constriction (TAC, n=6) for 10 weeks, examined by speckle‐tracking echocardiography and left ventricle (LV) pressure catheter, and portions of the LV were processed for biomarkers and histological analysis. In TAC mice as compared to Sham, Masson's Trichrome staining revealed an increase in fibrosis by 800% (P<0.01); with the majority of the collagen located in the mid‐wall of the myocardium. LV insoluble collagen hydroxyproline (HDXP) increased by 99% (P<0.01); and the collagen cross‐linker pyridinoline (PYD) increased by 100% (P<0.001). Tau was increased by 46% (P<0.01) and diastolic radial and circumferential strain rates were decreased by 41% and 44%, respectively (both P<0.01). The correlations between PYD and diastolic dysfunction were: r = 0.79, 0.76, and 0.85 for Tau, radial and circumferential strain rates, respectively. Similar correlations were observed for HDXP and diastolic dysfunction. In summary, cardiac fibrosis and diastolic dysfunction are highly correlated in the mouse TAC model with diastolic circumferential strain rate better correlated with cardiac fibrosis, possibly due to the majority of the fibrosis being located in the mid‐wall, where myofibers are aligned circumferentially.