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Genome‐wide expression profiling of a rat acute volume overload model identifies a major inflammatory response associated with extracellular matrix homeostasis disorder
Author(s) -
Chen Yuanwen,
Zheng Junying,
Pat Betty,
Cain Laura,
Powell Pamela,
Husain Ahsan,
Dell’Italia Louis J
Publication year - 2008
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.22.1_supplement.923.4
Subject(s) - inflammation , extracellular matrix , chemokine , fibronectin , volume overload , cd14 , gene expression profiling , receptor , microbiology and biotechnology , medicine , immunology , biology , endocrinology , chemistry , gene expression , gene , genetics , heart failure
In acute volume overload (VO) produced by aorto‐caval fistula (ACF) in the rat, a substantial loss of interstitial collagen was observed within 12 hours. Prevention of acute collagen loss attenuated progressive chamber dilation. To investigate the transcriptional changes which may mediate acute collagen loss and latter adverse chamber dilation, we performed a genome‐wide transcriptional profiling of left ventricles from rats subjected to 1 day ACF or sham surgery. In the ACF group, a 44% decrease of collagen was observed. 112 transcripts were up‐regulated and 37 were down‐regulated (fold>=1.5 with P<0.05). About 15% transcripts were selected and verified by real‐time quantitative RT‐PCR and/or immunoblot. Ingenuity Pathways Analysis revealed that the major functions of the altered genes are leukocyte migration and adhesion(MCP‐1, CD14, CCN5, etc) , immune response and inflammatory disease(IL‐1 receptor antagonist, activin A, colony stimulating factor 1, osteoprotegerin, etc ), interleukin and chemokine signaling (CD16, CD32, chemokine(c‐c) motif ligand 7, 12, 13, 11, etc), as well as connective tissue disorder(CD200 receptor 1, MMP‐19, fibronectin 1, etc). Greater than 50% of genes with 2‐fold or higher change are involved in inflammation. These results support an important role of inflammation in mediating the interstitial collagen loss and LV dilation in the acute VO of ACF. Support: HL54816