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Dilated cardiomyopathy in aged cardiac‐specific EP4 receptor KO mice
Author(s) -
Harding Pamela,
Yang XiaoPing,
He Quan,
Yang James,
Shesely Ed,
LaPointe Margot C
Publication year - 2009
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.23.1_supplement.814.4
Subject(s) - medicine , ejection fraction , fibrosis , muscle hypertrophy , cardiomyopathy , cardiac function curve , endocrinology , dilated cardiomyopathy , cardiac fibrosis , phenotype , heart failure , histology , apoptosis , receptor , biology , gene , biochemistry
To determine if a cardiac phenotype develops in aged EP4 KO mice, we performed echocardiography to assess ejection fraction (EF) on 23‐33‐week‐old male KO and wild‐type (WT) littermates. Hearts were removed for histology to assess hypertrophy (MCSA), fibrosis (ICF) and macrophage infiltration. WT mice had normal EF ( 80 ± 0.6%, n=70), whereas KO mice had a lower EF (60 ± 2.7%, n=55, p<0.001) coupled with left ventricular dilatation. MCSA and infiltrating macrophages were not different between groups but ICF increased by 35% in KO mice. In the KO mice, half had an EF below 60% and half above [EF in KO‐high function group (77 ± 1.3%, n=28) vs EF in KO‐low group (42.5 ± 2.4%, n=27); p<0.001]. In contrast to male KO mice, female KO mice had no cardiac phenotype through 28 weeks of age. Whole genome gene expression profiling (Illumina Mouse WG‐6 v2 chips) on hearts of 30‐32 week old male WT and KO mice indicated that 1100 genes were significantly differentially expressed. Of the 593 genes over expressed in the KO heart, many were involved in cardiac remodeling, apoptosis, calcium handling and cell signaling, with quantitative differences between KO low vs high function groups. In conclusion, the absence of EP4 in cardiac myocytes in a subgroup of aged male KO mice is associated with increased fibrosis, reduced EF and dilated cardiomyopathy.