Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Analysis of Ppif-/- hearts

ABSTRACT: To identify differences in gene expression between peptidylprolyl isomerase F (cyclophilin D; Ppif)-null hearts and WT control hearts. RNA was isolated from mice 8 weeks of age to discover gene changes prior to myocardial dysfunction. Three replicates each of Ppif-/- and WT mice.

ORGANISM(S): Mus musculus

SUBMITTER: John Elrod

PROVIDER: E-GEOD-23028 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice.

Elrod John W JW Wong Renee R Mishra Shikha S Vagnozzi Ronald J RJ Sakthievel Bhuvana B Goonasekera Sanjeewa A SA Karch Jason J Gabel Scott S Farber John J Force Thomas T Brown Joan Heller JH Murphy Elizabeth E Molkentin Jeffery D JD

The Journal of clinical investigation 20100920 10

Cyclophilin D (which is encoded by the Ppif gene) is a mitochondrial matrix peptidyl-prolyl isomerase known to modulate opening of the mitochondrial permeability transition pore (MPTP). Apart from regulating necrotic cell death, the physiologic function of the MPTP is largely unknown. Here we have shown that Ppif(-/-) mice exhibit substantially greater cardiac hypertrophy, fibrosis, and reduction in myocardial function in response to pressure overload stimulation than control mice. In addition, ...[more]

PMID: 20890047

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Project description:Rationale: The Id1 and Id3 genes play major roles during cardiac development, despite their expression being confined to non-myocardial layers (endocardium â?? endothelium - epicardium). We previously described that Id1â??/â??Id3â??/â?? double knockout (dKO) mouse embryos die at mid-gestation from multiple cardiac defects, but early demise precluded the studies of the roles of Id in the adult mice. Objective: To elucidate postnatal roles of Id genes in the heart. Methods and Results: We ablated Id1 gene in the vasculature and Id3 gene globally to generate Tie2Cre+Id1F/â??Id3â??/â?? and Tie2Cre+Id1F/FId3â??/â?? conditional KO (Id cKO) embryos. Half of the Id cKO mice die at birth. Postnatal demise was associated with cardiac underdevelopment, enlargement, muscular ventricular septal and endothelial defects. Surviving Id cKO mice exhibited dilated, fibrotic cardiomyopathy associated with defects in the vasculature. The adult cardiac phenotype progressed into heart failure and resembled endomyocardial fibroelastosis. An abnormal vascular response was also observed in the healing process of excisional skin wounds of Id cKO mice. Expression patterns of vascular, fibrotic and hypertrophic markers were altered in the Id cKO hearts, but addition of Insulin-Like Growth Factor binding protein-3 (IGFbp3) reversed gene expression profiles of vascular and fibrotic, but not hypertrophic markers. Conclusions: Conditional ablation of Id genes in the vasculature leads to dilated fibrotic cardiomyopathy. The findings could reveal important insights into the role(s) of the endocardial network of the endothelial lineage to the development of dilated fibrotic cardiomyopathy and identify a potential therapeutic target, IGFbp3, in its treatment. Total RNA from heart tissue was isolated (RNeasy, QIAGEN) from P180 WT, Id control, Id cKO, IGFbp3 incubated Id cKO, and control incubated Id cKO. RNA was converted to cDNA, cRNA, and hybridized to DNA sequences contained in the GeneChip Mouse Gene 1.0 ST Array (Affymetrix). Information from at least duplicate samples was compared and filtered by fold change >2 (Id cKO vs WT, Id control vs WT, IGFbp3 incubated Id cKO vs. control incubated Id cKO) and statistical p-value<0.001.

Dataset Information

Analysis of Ppif-/- hearts

Publications

Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice.

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