Deficiency of different nitric oxide synthase isoforms activates divergent transcriptional programs in cardiac hypertrophy

Thomas P. Cappola, Leslie Cope, Amy Cernetich, Lili A. Barouch, Khalid Minhas, Rafael A. Irizarry, Giovanni Parmigiani, Sarfraz Durrani, Tera Lavoie, Eric P. Hoffman, Shui Q. Ye, Joe G.N. Garcia, Joshua M. Hare

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Decreased nitric oxide synthase (NOS) activity induces left ventricular hypertrophy (LVH), but the transcriptional pathways mediating this effect are unknown. We hypothesized that specific NOS isoform deletion (NOS3 or NOS1) would activate different transcriptional programs in LVH. We analyzed cardiac expression profiles (Affymetrix MG-U74A) from NOS-/- mice using robust multi-array average (RMA). Of 12,422 genes analyzed, 47 genes were differentially expressed in NOS3-/- and 67 in NOS1-/- hearts compared with wild type (WT). Only 16 showed similar changes in both NOS-/- strains, most notably decreased heat-shock proteins (HSP10, 40, 70, 86, 105). Hypertrophied NOS1-/- hearts had unique features, including decreased myocyte-enriched calcineurin interacting protein and paradoxical downregulation of fetal isoforms (α-skeletal actin and brain natriuretic peptide). Cluster analyses demonstrated that NOS1 deletion caused more pronounced changes in the myocardial transcriptome than did NOS3 deletion, despite similar cardiac phenotypes. These findings suggest that the transcriptional basis for LVH varies depending on the inciting biochemical stimulus. In addition, NOS isoforms appear to play distinct roles in modulating cardiac structure.

Original languageEnglish (US)
Pages (from-to)25-34
Number of pages10
JournalPhysiological Genomics
StatePublished - Oct 2003


  • Gene expression profiling
  • Genomics
  • Knockout
  • Mice
  • Ventricular remodeling

ASJC Scopus subject areas

  • Physiology
  • Genetics


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