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Differential Role of p38α in the Cardiomyopathy Induced by Either β 1 ‐ or β 2 ‐Adrenergic Receptor Overexpression
Author(s) -
Peter Pallavi S.,
Brady Jennifer E.,
Chen Wei,
Chandra Rachna,
Liu Jing,
Thaisz Jill,
Yang Guiping,
Sadoshima Junichi,
Engelhardt Stefan,
Lohse Martin J.,
Wang Yibin,
Vatner Stephen F.,
Vatner Dorothy E.
Publication year - 2006
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.20.4.a311
Subject(s) - sirius red , medicine , cardiomyopathy , ejection fraction , endocrinology , cardiac fibrosis , fibrosis , myocardial fibrosis , cardiac function curve , heart failure
The goal of this study was to determine if p38α MAP kinase is implicated in the cardiomyopathy in transgenic (TG) mice with β 1 ‐ or β 2 ‐ adrenergic receptor (AR) overexpression. We examined mice with β 1 ‐AR and β 2 ‐AR overexpression (β 1 ‐AR TG and β 2 ‐AR TG), which exhibit enhanced left ventricular (LV) function as young adults (4–5 months) but develop impaired LV function and cardiomyopathy as they age and also examined these mice crossed with p38α dominant negative (DN) mice. In β 1 ‐AR TG, 11–15 months, LVEF was reduced, p<0.05, (54 ± 2%) vs WT (70 ± 1%) and cardiac fibrosis as reflected by Picric Sirius Red staining was enhanced (6.9 ± 1.3%) vs WT (0.5 ± 0.4%). Similarly, in β 2 ‐AR TG, 11–15 months, LVEF was reduced, p<0.05, (52 ± 3%) vs WT (70 ± 2%) and cardiac fibrosis was enhanced (5.2 ± 0.4%) vs WT (0.5 ± 0.4%). In bigenic mice, (β 1 ‐AR TG x p38αDN), 11–15 months, LVEF was depressed similarly to β 1 ‐AR TG (55 ± 3%) vs WT (70 ± 1%) and cardiac fibrosis was also not improved (5.9 ± 1.1%) vs WT (0.5 ± 0.4%). In contrast, in bigenic mice (β 2 ‐AR TG x p38αDN), 11–15 months, LVEF was rescued (81 ± 2%) vs WT (70 ± 2%) and cardiac fibrosis was attenuated, p<0.05, (3.5 ± 0.5%) vs WT (0.5 ± 0.4%). These results support the hypothesis that the cardiomyopathy, which develops in mice overexpressing β 1 ‐AR does not involve the adverse effects of enhanced p38α MAP kinase signaling, but the cardiomyopathy which develops in mice overexpressing β 2 ‐AR is mediated, at least in part, by p38α signaling.