Role of nitric oxide in matrix remodeling in diabetes and heart failure.
Accumulation of oxidized-matrix between the endothelium and myocytes is associated with endocardial endothelial (EE) dysfunction in diabetes and heart failure. High levels of circulating homocysteine (Hcy) have been demonstrated in diabetes mellitus (DM). These high levels of Hcy (hyperhomocysteinemia, HHcy) have a negative correlation with peroxisome proliferator activated receptor (PPAR) expression. Studies have demonstrated that Hcy decreases bioavailability of endothelial nitric oxide (eNO), generates nitrotyrosine, and activates latent matrix metalloproteinase (MMP), instigating EE dysfunction. PPAR ligands ameliorate endothelial dysfunction and DM. In addition Hcy competes with PPAR ligands. The understanding of molecular, cellular, and extracellular mechanisms by which Hcy amplifies DM will have therapeutic ramifications for diabetic cardiomyopathy.
Tyagi
Suresh C
SC
Department of Physiology and Biophysics, The University of Mississippi Medical Center, Jackson, MS 39216-4505, USA. styagi@physiology.umsmed.edu
Hayden
Melvin R
MR
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D006710:Homocysteine; D009569:Nitric Oxide; D020782:Matrix Metalloproteinases