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Changes in the mouse cardiac transcriptome post‐myocardial infarction predict disruption of L‐arginine metabolism
Author(s) -
Thomas D. Paul,
Harpster Mark H,
Bandyopadhyay Somnath,
Keele Jacque A,
McCormick Richard J,
Stayton Mark M
Publication year - 2007
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.21.6.a1405
Subject(s) - arginase , arginine , nitric oxide synthase , transcriptome , myocardial infarction , nitric oxide , polyamine , downregulation and upregulation , medicine , chemistry , endocrinology , gene expression , biochemistry , gene , amino acid
We surveyed mouse left ventricular (LV) transcriptome (36,899 transcripts) response to acute myocardial infarction (AMI) in the ischemic/infarcted freewall (IF), the surviving LV free wall (FW) and the interventricular septum (IVS). At six time points post‐AMI (15 min to 48 hr), transcripts were assayed in both AMI‐ and sham‐surgery mice. We identified 515 AMI‐responsive genes in the IF zone, 35 in FW, 7 in IVS with three genes induced in all three regions. Increases in steady‐state transcript levels were observed in the IF for l ‐arginase 1, l ‐arginase 2, four enzymes of polyamine biosynthesis and a protein inhibitor of nitric oxide synthase. The degree of induction of AMI‐responsive genes was significantly higher in IF vs. FW vs. IVS. For example, l ‐arginase 1 was induced 121‐fold within the IF, 60‐fold in the FW and 8‐fold in the IVS. None of the nitric oxide synthase (NOS) isozymes showed transcriptional upregulation (p<0.05) within any LV region at any of the measured time‐points. Thus NO production may be regulated, in part, by inhibition of NOS and coordinate depletion of the NOS substrate, l ‐arginine. Alternatively, NOS and l ‐arginase may draw from separate pools of l ‐arginine. In the latter scenario, l ‐arginase 1 induction would function primarily to drive proline biosynthesis and polyamine production. Support: NIH grants P20 RR15640 and R15 HL71239